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Information on EC 2.3.1.B43 - protein-lysine desuccinylase (NAD+)
for references in articles please use BRENDA:EC2.3.1.B43
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preliminary BRENDA-supplied EC number
EC Tree 2 Transferases
2.3 Acyltransferases
2.3.1 Transferring groups other than aminoacyl groups
2.3.1.B43 protein-lysine desuccinylase (NAD+)
The expected taxonomic range for this enzyme is: Archaea, Eukaryota, Bacteria
- 2.3.1.B43
- sirtuins
- sirt3
-
deacetylation
- deacetylases
-
desuccinylation
-
malonylation
-
nad-dependent
-
sirt1-7
-
glutarylation
- diagnostics
- medicine
- drug development
Reaction Schemes
show+
+
=
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+
Synonyms
sirt5, sirtuin 5, nad+-dependent protein deacetylase, nad+ dependent deacetylase, nicotinamide adenine dinucleotide-dependent protein deacetylase, sirtuin deacylase, histone desuccinylase, nad+-dependent protein deacylase, lysine desuccinylase, nad+-dependent sirtuin deacetylase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CobB
lysine desuccinylase
NAD+-dependent protein deacetylase
nicotinamide adenine dinucleotide-dependent protein deacetylase
SIRT5
SIRT5iso1
SIRT5iso2
sirtuin 5
sirtuin 5 deacylase
sirtuin deacylase
SIRT5
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728857, 729138, 729372, 729547, 729885, 729993, 730024, 730205, 730245, 730474, 730706, 730713, 730922, 730964, 730974, 731010, 738843, 739445, 755788, 755970, 756010, 756427, 756522, 756680, 757175, 757350, 757400, 757590, 758247, 776863, 776943, 776985, 777265, 777320, 777423, 778071, 778258, 779416
SIRT5
SIRT5 isoforms (i.e., SIRT5iso1 and SIRT5iso2) are encoded by the human SIRT5 gene. Their C-termini slightly differ from each other. Although both isoforms contain cleavable mitochondrial targeting signals at their N-termini, it is found that the cleaved SIRT5iso2 is localized mainly in mitochondria, whereas the cleaved SIRT5iso1 is localized in both mitochondria and cytoplasm
SIRT5
-
SIRT5iso1
SIRT5 isoforms (i.e., SIRT5iso1 and SIRT5iso2) are encoded by the human SIRT5 gene. Their C-termini slightly differ from each other. Although both isoforms contain cleavable mitochondrial targeting signals at their N-termini, it is found that the cleaved SIRT5iso2 is localized mainly in mitochondria, whereas the cleaved SIRT5iso1 is localized in both mitochondria and cytoplasm
SIRT5iso2
SIRT5 isoforms (i.e., SIRT5iso1 and SIRT5iso2) are encoded by the human SIRT5 gene. Their C-termini slightly differ from each other. Although both isoforms contain cleavable mitochondrial targeting signals at their N-termini, it is found that the cleaved SIRT5iso2 is localized mainly in mitochondria, whereas the cleaved SIRT5iso1 is localized in both mitochondria and cytoplasm. SIRT5iso2 is a primate-specific isoform
sirtuin 5
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
NAD+ + [protein]-N6-acetyl-L-lysine + H2O = nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP-ribose
NAD+ + [protein]-N6-succinyl-L-lysine + H2O = nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
NAD+ + [protein]-N6-acetyl-L-lysine + H2O = nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP-ribose
crystallographic evidence is provided that 2'-O-acetyl ADP-ribose is a final product in the Sir2 reaction. A revised mechanism for catalysis based on the structural and functional characterization of Sir2 mutants is proposed. In this mechanism, the activation of the 2'-OH of nicotinamide ribose by His-116 is essential for the hydrolysis of the acetyl groups from N-acetyl lysine. The conserved Ser-24 and Asp-101 participate in the stabilization of local structure for NAD binding rather than direct involvement in catalysis
NAD+ + [protein]-N6-acetyl-L-lysine + H2O = nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP-ribose
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NAD+ + [protein]-N6-succinyl-L-lysine + H2O = nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
most efficient at catalyzing desuccinylation, medium-chain deacylation (octanoyl-, decanoyl-, dodecanoyl-) is catalyzed with lower activity
NAD+ + [protein]-N6-succinyl-L-lysine + H2O = nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
CH3CONH-AR-[Nepsilon-succinyl-lysine]-ST-CONH2 + NAD+ + H2O
CH3CONH-ARKST-CONH2 + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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?
Fluor de Lys-succinyl + NAD+ + H2O
Fluor de Lys + 2''O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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?
NAD+ + Abz-GVLK(glutaryl)AY(NO2)GV-NH2 + H2O
nicotinamide + ?
Substrates: -
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?
NAD+ + Ac-(N6-methylmalonyl)Lys-(7-amido-4-methylcoumarin) + H2O
nicotinamide + Ac-Lys-7-amido-4-methylcoumarin + 2'-O-methylmalonyl-ADP-ribose
Substrates: -
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NAD+ + Ac-(N6-succinyl)Lys-7-amido-4-methylcoumarin + H2O
nicotinamide + Ac-Lys-7-amido-4-methylcoumarin + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + Ac-Leu-Gly-(N6-malonyl)Lys-7-amido-4-methylcoumarin + H2O
nicotinamide + Ac-Leu-Gly-Lys-7-amido-4-methylcoumarin + 2'-O-malonyl-ADP-ribose
Substrates: -
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NAD+ + Ac-Leu-Gly-(N6-succinyl)Lys-7-amido-4-methylcoumarin + H2O
nicotinamide + Ac-Leu-Gly-Lys-7-amido-4-methylcoumarin + 2'-O-succinyl-ADP-ribose
Substrates: -
Products: -
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?
NAD+ + Ac-Suc-L-Lys-7-amido-4-methylcoumarin + H2O
nicotinamide + ?
Substrates: -
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?
NAD+ + AFNQG(N6-malonyl)KIFK + H2O
nicotinamide + AFNQGKIFK + 2'-O-malonyl-ADP-ribose
Substrates: -
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NAD+ + AYVDDTPAEQM(N6-malonyl)KAER + H2O
nicotinamide + AYVDDTPAEQMKAER + 2'-O-malonyl-ADP-ribose
Substrates: -
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NAD+ + benzoyl-GVL(N6-acetyl)KEYGV-amide + H2O
nicotinamide + benzoyl-GVLKEYGV-amide + 2'-O-acetyl-ADP-ribose
Substrates: -
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NAD+ + benzoyl-GVL(N6-adipoyl)KEYGV-amide + H2O
nicotinamide + benzoyl-GVLKEYGV-amide + 2'-O-adipoyl-ADP-ribose
Substrates: -
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NAD+ + benzoyl-GVL(N6-glutaryl)KEYGV-amide + H2O
nicotinamide + benzoyl-GVLKEYGV-amide + 2'-O-glutaryl-ADP-ribose
Substrates: -
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NAD+ + benzoyl-GVL(N6-malonyl)KEYGV-amide + H2O
nicotinamide + benzoyl-GVLKEYGV-amide + 2'-O-malonyl-ADP-ribose
Substrates: -
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?
NAD+ + benzoyl-GVL(N6-oxalyl)KEYGV-amide + H2O
nicotinamide + benzoyl-GVLKEYGV-amide + 2'-O-oxalyl-ADP-ribose
Substrates: -
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NAD+ + benzoyl-GVL(N6-pimeloyl)KEYGV-amide + H2O
nicotinamide + benzoyl-GVLKEYGV-amide + 2'-O-pimeloyl-ADP-ribose
Substrates: -
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NAD+ + benzoyl-GVL(N6-suberoyl)KEYGV-amide + H2O
nicotinamide + benzoyl-GVLKEYGV-amide + 2'-O-suberoyl-ADP-ribose
Substrates: -
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NAD+ + benzoyl-GVL(N6-succinyl)KEYGV-amide + H2O
nicotinamide + benzoyl-GVLKEYGV-amide + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + benzoyl-RGVL(N6-succinyl)KEYGV-amide + H2O
nicotinamide + benzoyl-RGVLKEYGV-amide + 2'-O-acetyl-ADP-ribose
Substrates: carbamoyl phosphate synthetase 1 Lys527 peptide
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NAD+ + benzyl-(N6-succinyl)Lys-7-amido-4-methylcoumarin + H2O
nicotinamide + benzyl-Lys-7-amido-4-methylcoumarin + 2'-O-succinyl-ADP-ribose
Substrates: fluorogenic substrate
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NAD+ + DSYVGDEAQSDSYVGDEAQS(N6-malonyl)KR + H2O
nicotinamide + DSYVGDEAQSDSYVGDEAQSKR + 2'-O-malonyl-ADP-ribose
Substrates: -
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NAD+ + ETGVDLT(N6-succinyl)KDNMALQR + H2O
nicotinamide + ETGVDLTKDNMALQR + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + FKRGVL(N6-acetyl)KEYGVKV + H2O
nicotinamide + FKRGVLKEYGVKV + 2'-O-acetyl-ADP-ribose
NAD+ + IEEELGS(N6-malonyl)KAK + H2O
nicotinamide + IEEELGSKAK + 2'-O-malonyl-ADP-ribose
Substrates: -
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NAD+ + KGLGKGGA(N6-acetyl)KRHRKW + H2O
nicotinamide + KGLGKGGAKRHRKW + 2'-O-acetyl-ADP-ribose
NAD+ + KGLGKGGA(N6-butyryl)KRHRKW + H2O
nicotinamide + KGLGKGGAKRHRKW + 2'-O-butyryl-ADP-ribose
NAD+ + KGLGKGGA(N6-propionyl)KRHRKW + H2O
nicotinamide + KGLGKGGAKRHRKW + 2'-O-propionyl-ADP-ribose
NAD+ + KGLGKGGA(N6-succinyl)KRHRKW + H2O
nicotinamide + KGLGKGGAKRHRKW + 2'-O-succinyl-ADP-ribose
NAD+ + KQTAR(N6-malonyl)KSTGGWW + H2O
nicotinamide + KQTARKSTGGWW + 2'-O-malonyl-ADP-ribose
Substrates: histone H3K9 malonyl peptide
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NAD+ + KQTAR(N6-succinyl)KSTGGKA + H2O
nicotinamide + KQTARKSTGGKA + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + KQTAR(N6-succinyl)KSTGGWW + H2O
nicotinamide + KQTARKSTGGWW + 2'-O-succinyl-ADP-ribose
Substrates: histone H3K9 succinyl peptide
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NAD+ + KTRSG(N6-malonyl)KVMRRWW + H2O
nicotinamide + KTRSGKVMRRWW + 2'-O-malonyl-ADP-ribose
Substrates: -
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NAD+ + KTRSG(N6-succinyl)KVMRRWW + H2O
nicotinamide + KTRSGKVMRRWW + 2'-O-succinyl-ADP-ribose
Substrates: ACS2 Lys628 peptide
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NAD+ + N2-benzyloxycarbonyl-N6-succinyl-L-lysine-7-amido-4-methylcoumarin + H2O
nicotinamide + N2-benzyloxycarbonyl-L-lysine-7-amido-4-methylcoumarin + 2'-O-succinyl-ADP-ribose
Substrates: i.e. 3-[(5-[[(benzyloxy)carbonyl]amino]-5-[(4-methyl-2-oxo-2H-chromen-7-yl)carbamoyl]pentyl)carbamoyl]-propanoic acid
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NAD+ + QTAR(N6-acetyl)KSTGG + H2O
nicotinamide + QTARKSTGG + 2'-O-acetyl-ADP-ribose
Substrates: acetylated histone H3 peptide, less than 10% compared to the activity with the succinylated peptide
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NAD+ + QTAR(N6-decanoyl)KSTGG + H2O
nicotinamide + QTARKSTGG + 2'-O-decanoyl-ADP-ribose
Substrates: decanoylated histone H3 peptide, about 35% compared to the activity with the succinylated peptide
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NAD+ + QTAR(N6-dodecanoyl)KSTGG + H2O
nicotinamide + QTARKSTGG + 2'-O-dodecanoyl-ADP-ribose
Substrates: dodecanoylated histone H3 peptide, about 35% compared to the activity with the succinylated peptide
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NAD+ + QTAR(N6-hexanoyl)KSTGG + H2O
nicotinamide + QTARKSTGG + 2'-O-hexanoyl-ADP-ribose
Substrates: hexanoylated histone H3 peptide, less than 10% compared to the activity with the succinylated peptide
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NAD+ + QTAR(N6-myristoyl)KSTGG + H2O
nicotinamide + QTARKSTGG + 2'-O-myristoyl-ADP-ribose
Substrates: myristoylated histone H3 peptide, about 15% compared to the activity with the succinylated peptide
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NAD+ + QTAR(N6-octanoyl)KSTGG + H2O
nicotinamide + QTARKSTGG + 2'-O-octanoyl-ADP-ribose
Substrates: octanoylated histone H3 peptide, about 30% compared to the activity with the succinylated peptide
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NAD+ + QTAR(N6-propionyl)KSTGG + H2O
nicotinamide + QTARKSTGG + 2'-O-propionyl-ADP-ribose
Substrates: propionylated histone H3 peptide, less than 10% compared to the activity with the succinylated peptide
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NAD+ + QTAR(N6-succinyl)KSTGG + H2O
nicotinamide + QTARKSTGG + 2'-O-succinyl-ADP-ribose
Substrates: succinylated histone H3 peptide
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NAD+ + SGASE(N6-malonyl)KDIVHSGWW + H2O
nicotinamide + SGASEKDIVHSGWW + 2'-O-malonyl-ADP-ribose
Substrates: -
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NAD+ + SGASE(N6-succinyl)KDIVHSGWW + H2O
nicotinamide + SGASEKDIVHSGWW + 2'-O-succinyl-ADP-ribose
Substrates: glutamate dehydrogenase Lys503 peptide
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NAD+ + SKEYFS(N6-succinyl)KQK + H2O
nicotinamide + SKEYFSKQK + 2'-O-acetyl-ADP-ribose
Substrates: -
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NAD+ + SQG(N6-succinyl)KVLQATVV + H2O
nicotinamide + SQGKVLQATVV + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + TAIG(N6-malonyl)KAGYTDK + H2O
nicotinamide + TAIGKAGYTDK + 2'-O-malonyl-ADP-ribose
Substrates: -
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NAD+ + TRSG(N6-acetyl)KVMR + H2O
nicotinamide + TRSGKVMR + 2'-O-acetyl-ADP-ribose
Substrates: peptide based on an acetyl-CoA synthetase 2 acetylation site
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NAD+ + VLLPEYGGT(N6-succinyl)KVVLDDK + H2O
nicotinamide + VLLPEYGGTKVVLDDK + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [acetyl-coenzyme A synthetase]-N6-acetyl-L-lysine609 + H2O
nicotinamide + [acetyl-coenzyme A synthetase]-L-lysine609 + 2'-O-acetyl-ADP-ribose
NAD+ + [ATP synthase]-N6-succinyl-L-lysine + H2O
nicotinamide + [ATP synthase]-L-lysine + 2'-O-succinyl-ADP-ribose
NAD+ + [bovine serum albumin]-N6-acetyl-L-lysine + H2O
nicotinamide + [bovine serum albumin]-L-lysine + 2'-O-acetyl-ADP-ribose
Substrates: crystallographic evidence is provided that 2'-O-acetyl ADP-ribose is a final product in the Sir2 reaction. A revised mechanism for catalysis based on the structural and functional characterization of Sir2 mutants is proposed. In this mechanism, the activation of the 2'-OH of nicotinamide ribose by His-116 is essential for the hydrolysis of the acetyl groups from N-acetyl lysine. The conserved Ser-24 and Asp-101 participate in the stabilization of local structure for NAD binding rather than direct involvement in catalysis
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NAD+ + [carbamoyl phosphate synthase 1]-N6-acetyl-L-lysine + H2O
nicotinamide + [carbamoyl phosphate synthase 1]-L-lysine + 2'-O-acetyl-ADP ribose
NAD+ + [carbamoyl phosphate synthase 1]-N6-acetyl-L-lysine + H2O
nicotinamide + [carbamoyl phosphate synthase 1]-L-lysine + 2'-O-acetyl-ADP-ribose
NAD+ + [carbamoyl phosphate synthase 1]-N6-succinyl-L-lysine + H2O
nicotinamide + [carbamoyl phosphate synthase 1]-L-lysine + 2'-O-succinyl-ADP ribose
Substrates: deletion of Sirt5 in mice increases the level of succinylation on carbamoyl phosphate synthase 1
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NAD+ + [carbamoyl phosphate synthetase 1 derived glutarylated peptide]-N6-acetyl-L-lysine + H2O
nicotinamide + [carbamoyl phosphate synthetase 1 derived glutarylated peptide]-L-lysine + 2'-O-acetyl-ADP-ribose
Substrates: -
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NAD+ + [carbamoyl phosphate synthetase 1]-N6-acetyl-L-lysine + H2O
nicotinamide + [carbamoyl phosphate synthetase 1]-L-lysine + 2'-O-acetyl-ADP ribose
NAD+ + [carbamoyl phosphate synthetase 1]-N6-glutaryl-L-lysine + H2O
nicotinamide + [carbamoyl phosphate synthetase 1]-L-lysine + 2'-O-glutaryl-ADP-ribose
Substrates: -
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NAD+ + [chicken histone]-N6-acetyl-L-lysine + H2O
nicotinamide + [chicken histone]-L-lysine + 2'-O-acetyl-ADP-ribose
Substrates: chemically acetylated chicken histone. Less activity toward chemically acetylated bovine serum albumin and monoacetylated histone H4 (K16 and K8). No activity is observed with monoacetylated histone K5 and K12 histone H4 peptides
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NAD+ + [Cu/Zn superoxide dismutase]-N6-succinyl-L-lysine123 + H2O
nicotinamide + [Cu/Zn superoxide dismutase]-L-lysine123 + 2'-O-succinyl-ADP-ribose
NAD+ + [cytochrome c]-N6-acetyl-L-lysine + H2O
nicotinamide + [cytochrome c]-L-lysine + 2'-O-acetyl-ADP-ribose
Substrates: -
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NAD+ + [forkhead box O3]-N6-acetyl-L-lysine + H2O
nicotinamide + [forkhead box O3]-L-lysine + 2'-O-acetyl-ADP-ribose
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Substrates: the enzyme deacetylates FOXO3 at K271 and K290
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NAD+ + [glucose 6-phosphate dehydrogenase]-N6-succinyl-L-lysine + H2O
nicotinamide + [glucose 6-phosphate dehydrogenase]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [glucose-6-phosphate dehydrogenase]-N6-acetyl-L-lysine + H2O
nicotinamide + [glucose-6-phosphate dehydrogenase]-L-lysine + 2'-O-acetyl-ADP-ribose
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Substrates: -
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NAD+ + [glutaminase]-N6-succinyl-L-lysine + H2O
nicotinamide + [glutaminase]-L-lysine + 2'-O-succinyl-ADP-ribose
NAD+ + [glyceraldehyde-3-phosphate dehydrogenase]-N6-malonyl-L-lysine + H2O
nicotinamide + [glyceraldehyde-3-phosphate dehydrogenase]-L-lysine + 2'-O-malonyl-ADP-ribose
Substrates: -
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NAD+ + [histone H2A]-N6-succinyl-L-lysine95 + H2O
nicotinamide + [histone H2A]-L-lysine95 + 2'-O-succinyl-ADP-ribose
Substrates: complete desuccinylation
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NAD+ + [histone H2A]-N6-succinyl-L-lysine9_(4-15)-A10G peptide + H2O
nicotinamide + [histone H2A]-L-lysine9_(4-15)-A10G peptide + 2'-O-succinyl-ADP-ribose
Substrates: partial desuccinylation, mutant peptide substrate
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NAD+ + [histone H2B]-N6-succinyl-L-lysine116 + H2O
nicotinamide + [histone H2B]-L-lysine116 + 2'-O-succinyl-ADP-ribose
Substrates: complete desuccinylation
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NAD+ + [histone H2B]-N6-succinyl-L-lysine120 + H2O
nicotinamide + [histone H2B]-L-lysine120 + 2'-O-succinyl-ADP-ribose
Substrates: complete desuccinylation
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NAD+ + [histone H2B]-N6-succinyl-L-lysine34 + H2O
nicotinamide + [histone H2B]-L-lysine34 + 2'-O-succinyl-ADP-ribose
Substrates: complete desuccinylation
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NAD+ + [histone H2B]-N6-succinyl-L-lysine9 + H2O
nicotinamide + [histone H2B]-L-lysine9 + 2'-O-succinyl-ADP-ribose
NAD+ + [histone H3 K9 peptide]-N6-acetyl-L-lysine + H2O
nicotinamide + [histone H3 K9 peptide]-L-lysine + 2'-O-acetyl-ADP-ribose
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Substrates: -
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NAD+ + [histone H3 K9 peptide]-N6-succinyl-L-lysine + H2O
nicotinamide + [histone H3 K9 peptide]-L-lysine + 2'-O-succinyl-ADP-ribose
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Substrates: -
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NAD+ + [histone H3]-N6-succinyl-L-lysine122 + H2O
nicotinamide + [histone H3]-L-lysine122 + 2'-O-succinyl-ADP-ribose
Substrates: complete desuccinylation
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NAD+ + [histone H3]-N6-succinyl-L-lysine14 + H2O
nicotinamide + [histone H3]-L-lysine14 + 2'-O-succinyl-ADP-ribose
Substrates: partial desuccinylation, low activity
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NAD+ + [histone H3]-N6-succinyl-L-lysine14_(9-20)-A15G peptide + H2O
nicotinamide + [histone H3]-L-lysine14_(9-20)-A15G peptide + 2'-O-succinyl-ADP-ribose
Substrates: partial desuccinylation, mutant peptide substrate
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NAD+ + [histone H3]-N6-succinyl-L-lysine56 + H2O
nicotinamide + [histone H3]-L-lysine56 + 2'-O-succinyl-ADP-ribose
Substrates: complete desuccinylation
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NAD+ + [histone H3]-N6-succinyl-L-lysine79 + H2O
nicotinamide + [histone H3]-L-lysine79 + 2'-O-succinyl-ADP-ribose
Substrates: partial desuccinylation
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NAD+ + [histone H3]-N6-succinyl-L-lysine9 + H2O
nicotinamide + [histone H3]-L-lysine9 + 2'-O-succinyl-ADP-ribose
Substrates: complete desuccinylation
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NAD+ + [histone H4]-N6-acetyl-L-lysine16 + H2O
nicotinamide + [histone H4]-L-lysine16 + 2'-O-acetyl-ADP-ribose
Substrates: deacetylation, cf. EC 2.3.1.286
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NAD+ + [histone H4]-N6-succinyl-L-lysine12 + H2O
nicotinamide + [histone H4]-L-lysine12 + 2'-O-succinyl-ADP-ribose
Substrates: partial desuccinylation
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NAD+ + [histone H4]-N6-succinyl-L-lysine31 + H2O
nicotinamide + [histone H4]-L-lysine31 + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [histone H4]-N6-succinyl-L-lysine31_(26-37)-P32A peptide + H2O
nicotinamide + [histone H4]-L-lysine31_(26-37)-P32A peptide + 2'-O-succinyl-ADP-ribose
Substrates: partial desuccinylation, mutant peptide substrate
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NAD+ + [histone H4]-N6-succinyl-L-lysine77 + H2O
nicotinamide + [histone H4]-L-lysine77 + 2'-O-succinyl-ADP-ribose
Substrates: almost complete desuccinylation
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NAD+ + [histone H4]-N6-succinyl-L-lysine91 + H2O
nicotinamide + [histone H4]-L-lysine91 + 2'-O-succinyl-ADP-ribose
Substrates: complete desuccinylation
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NAD+ + [IDH2]-N6-succinyl-L-lysine + H2O
nicotinamide + [IDH2]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: i.e. isocitrate dehydrogenase [NADP+]
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NAD+ + [isocitrate dehydrogenase 2]-N6-acetyl-L-lysine + H2O
nicotinamide + [isocitrate dehydrogenase 2]-L-lysine + 2'-O-acetyl-ADP-ribose
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Substrates: -
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NAD+ + [N-hydroxyarylamine O-acetyltransferase]-N6-acetyl-L-lysine + H2O
nicotinamide + [N-hydroxyarylamine O-acetyltransferase]-L-lysine + 2'-O-acetyl-ADP-ribose
NAD+ + [peptide derived from carbamoyl phosphate synthetase 1]-N6-acetyl-L-lysine + H2O
nicotinamide + [peptide derived from carbamoyl phosphate synthetase 1]-L-lysine + 2'-O-acetyl-ADP-ribose
Substrates: -
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NAD+ + [protein]-N6-acetyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP-ribose
NAD+ + [protein]-N6-malonyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-malonyl-ADP-ribose
NAD+ + [protein]-N6-succinyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
NAD+ + [PrpE protein]-N6-acetyl-L-lysine + H2O
nicotinamide + [PrpE protein]-L-lysine + 2'-O-acetyl-ADP ribose
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Substrates: -
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NAD+ + [PrpE protein]-N6-propionyl-L-lysine + H2O
nicotinamide + [PrpE protein]-L-lysine + 2'-O-propionyl-ADP-ribose
NAD+ + [pyruvate dehydrogenase complex]-N6-succinyl-L-lysine + H2O
nicotinamide + [pyruvate dehydrogenase complex]-L-lysine + O-succinyl-ADP-ribose
NAD+ + [pyruvate kinase M2]-N6-succinyl-L-lysine311 + H2O
nicotinamide + [pyruvate kinase M2]-L-lysine311 + 2'-O-succinyl-ADP-ribose
NAD+ + [RcsB protein]-N6-acetyl-L-lysine180 + H2O
nicotinamide + [RcsB protein]-L-lysine180 + 2'-O-acetyl-ADP-ribose
NAD+ + [response regulator CheY]-N6-acetyl-L-lysine + H2O
nicotinamide + [response regulator CheY]-L-lysine + 2'-O-acetyl-ADP-ribose
NAD+ + [succinate dehydrogenase]-N6-succinyl-L-lysine + H2O
nicotinamide + [succinate dehydrogenase]-L-lysine + O-succinyl-ADP-ribose
NAD+ + [urate oxidase]-N6-acetyl-L-lysine + H2O
nicotinamide + [urate oxidase]-L-lysine + 2'-O-acetyl-ADP-ribose
[2-oxoglutarate dehydrogenase]-N6-succinyl-L-lysine + NAD+ + H2O
[2-oxoglutarate dehydrogenase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[acyl-CoA oxidase 1]-N6-succinyl-L-lysine + NAD+ + H2O
[acyl-CoA oxidase 1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[c-myc]-N6-succinyl-L-lysine + NAD+ + H2O
[c-myc]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[carbamoyl phosphate synthase 1]-N6-succinyl-L-lysine + NAD+ + H2O
[carbamoyl phosphate synthase 1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[COA6]-N6-succinyl-L-lysine + NAD+ + H2O
[COA6]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
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Substrates: -
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[COX12]-N6-succinyl-L-lysine + NAD+ + H2O
[COX12]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
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Substrates: -
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[COX5A]-N6-succinyl-L-lysine + NAD+ + H2O
[COX5A]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
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Substrates: -
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[COX5B]-N6-succinyl-L-lysine + NAD+ + H2O
[COX5B]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
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Substrates: -
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[enhanced trifunctional enzyme subunit-alpha]-N6-succinyl-L-lysine + NAD+ + H2O
[enhanced trifunctional enzyme subunit-alpha]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[GLS2]-N6-succinyl-L-lysine + NAD+ + H2O
[GLS2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[glucose-6-phosphate isomerase]-N6-succinyl-L-lysine + NAD+ + H2O
[glucose-6-phosphate isomerase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[glutaminase]-N6-succinyl-L-lysine + NAD+ + H2O
[glutaminase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[glutathione peroxidase Hyr1]-N6-succinyl-L-lysine + NAD+ + H2O
[glutathione peroxidase Hyr1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[histidine triad nucleotide binding protein 1]-N6-succinyl-L-lysine + NAD+ + H2O
[histidine triad nucleotide binding protein 1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[histone H3]-N6-succinyl-L-lysine + NAD+ + H2O
[histone H3]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[inosine-5'-monophosphate dehydrogenase]-N6-succinyl-L-lysine + NAD+ + H2O
[inosine-5'-monophosphate dehydrogenase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[isocitrate dehydrogenase 2]-N6-acetyl-L-lysine + NAD+ + H2O
[isocitrate dehydrogenase 2]-L-lysine + 2''-O-acetyl-ADP-D-ribose + nicotinamide
Substrates: -
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[isocitrate dehydrogenase 2]-N6-succinyl-L-lysine + NAD+ + H2O
[isocitrate dehydrogenase 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[lactate dehydrogenase A]-N6-succinyl-L-lysine + NAD+ + H2O
[lactate dehydrogenase A]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[mitochondrial antiviral signaling protein]-N6-succinyl-L-lysine + NAD+ + H2O
[mitochondrial antiviral signaling protein]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[mitochondrial glutaminase]-N6-succinyl-L-lysine + NAD+ + H2O
[mitochondrial glutaminase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[mitochondrial malic enzyme 2]-N6-succinyl-L-lysine + NAD+ + H2O
[mitochondrial malic enzyme 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[Ndufa2]-N6-succinyl-L-lysine + NAD+ + H2O
[Ndufa2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
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Substrates: -
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[Ndufa8]-N6-succinyl-L-lysine + NAD+ + H2O
[Ndufa8]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
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Substrates: -
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[Ndufs4]-N6-succinyl-L-lysine + NAD+ + H2O
[Ndufs4]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
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Substrates: -
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[Ndufs6]-N6-succinyl-L-lysine + NAD+ + H2O
[Ndufs6]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
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Substrates: -
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[p53]-N6-succinyl-L-lysine + NAD+ + H2O
[p53]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[PKM2]-N6-succinyl-L-lysine + NAD+ + H2O
[PKM2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[serine hydroxymethyltransferase 2]-N6-succinyl-L-lysine + NAD+ + H2O
[serine hydroxymethyltransferase 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[succinate dehydrogenase complex subunit A]-N6-succinyl-L-lysine + NAD+ + H2O
[succinate dehydrogenase complex subunit A]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[superoxide dismutase 1]-N6-acetyl-L-lysine + NAD+ + H2O
[superoxide dismutase 1]-L-lysine + 2''-O-acetyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 desuccinylates and activates SOD1, thereby exerting a key function in ROS detoxification
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[superoxide dismutase 1]-N6-succinal-L-lysine + NAD+ + H2O
[superoxide dismutase 1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 desuccinylates and activates SOD1, thereby exerting a key function in ROS detoxification
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[superoxide dismutase 1]-N6-succinyl-L-lysine + NAD+ + H2O
[superoxide dismutase 1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[TBK1]-N6-succinyl-L-lysine + NAD+ + H2O
[TBK1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[thioredoxin Trx2]-N6-succinyl-L-lysine + NAD+ + H2O
[thioredoxin Trx2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[ubiquinol-cytochrome C reductase core protein 2]-N6-succinyl-L-lysine + NAD+ + H2O
[ubiquinol-cytochrome C reductase core protein 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
NAD+ + FKRGVL(N6-acetyl)KEYGVKV + H2O
nicotinamide + FKRGVLKEYGVKV + 2'-O-acetyl-ADP-ribose
Substrates: carbamoyl phosphate synthetase 1 Lys527 peptide
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NAD+ + FKRGVL(N6-acetyl)KEYGVKV + H2O
nicotinamide + FKRGVLKEYGVKV + 2'-O-acetyl-ADP-ribose
Substrates: acetylated peptide derived from carbamoylphosphate synthetase 1 (CPS1)
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NAD+ + KGLGKGGA(N6-acetyl)KRHRKW + H2O
nicotinamide + KGLGKGGAKRHRKW + 2'-O-acetyl-ADP-ribose
Substrates: the rate of desuccinylation is about 5fold faster than the rate of deacetylation
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NAD+ + KGLGKGGA(N6-acetyl)KRHRKW + H2O
nicotinamide + KGLGKGGAKRHRKW + 2'-O-acetyl-ADP-ribose
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Substrates: the rate of desuccinylation is 2.3fold faster than the rate of deacetylation
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NAD+ + KGLGKGGA(N6-butyryl)KRHRKW + H2O
nicotinamide + KGLGKGGAKRHRKW + 2'-O-butyryl-ADP-ribose
Substrates: the rate of desuccinylation is about 10fold faster than the rate of debutyrylation
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NAD+ + KGLGKGGA(N6-butyryl)KRHRKW + H2O
nicotinamide + KGLGKGGAKRHRKW + 2'-O-butyryl-ADP-ribose
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Substrates: the rate of desuccinylation is 5.8fold faster than the rate of deburyrylation
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NAD+ + KGLGKGGA(N6-propionyl)KRHRKW + H2O
nicotinamide + KGLGKGGAKRHRKW + 2'-O-propionyl-ADP-ribose
Substrates: the rate of desuccinylation is about 5fold faster than the rate of depropionylation
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NAD+ + KGLGKGGA(N6-propionyl)KRHRKW + H2O
nicotinamide + KGLGKGGAKRHRKW + 2'-O-propionyl-ADP-ribose
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Substrates: the rate of desuccinylation is 3.8fold faster than the rate of depropionylation
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NAD+ + KGLGKGGA(N6-succinyl)KRHRKW + H2O
nicotinamide + KGLGKGGAKRHRKW + 2'-O-succinyl-ADP-ribose
Substrates: the rate of desuccinylation is about 5fold faster than the rate of deacetylation
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NAD+ + KGLGKGGA(N6-succinyl)KRHRKW + H2O
nicotinamide + KGLGKGGAKRHRKW + 2'-O-succinyl-ADP-ribose
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Substrates: the rate of desuccinylation is 2.3fold faster than the rate of deacetylation
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NAD+ + [acetyl-coenzyme A synthetase]-N6-acetyl-L-lysine609 + H2O
nicotinamide + [acetyl-coenzyme A synthetase]-L-lysine609 + 2'-O-acetyl-ADP-ribose
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Substrates: deacetylation by CobB activates the acetyl-coenzyme A synthetase
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NAD+ + [acetyl-coenzyme A synthetase]-N6-acetyl-L-lysine609 + H2O
nicotinamide + [acetyl-coenzyme A synthetase]-L-lysine609 + 2'-O-acetyl-ADP-ribose
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Substrates: -
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NAD+ + [ATP synthase]-N6-succinyl-L-lysine + H2O
nicotinamide + [ATP synthase]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [ATP synthase]-N6-succinyl-L-lysine + H2O
nicotinamide + [ATP synthase]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [carbamoyl phosphate synthase 1]-N6-acetyl-L-lysine + H2O
nicotinamide + [carbamoyl phosphate synthase 1]-L-lysine + 2'-O-acetyl-ADP ribose
Substrates: SIRT5 deacetylates carbamoyl phosphate synthetase 1 (CPS1), an enzyme which is the first and rate-limiting step of urea cycle. Deacetylation of CPS1 by SIRT5 results in activation of CPS1 enzymatic activity
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NAD+ + [carbamoyl phosphate synthase 1]-N6-acetyl-L-lysine + H2O
nicotinamide + [carbamoyl phosphate synthase 1]-L-lysine + 2'-O-acetyl-ADP ribose
Substrates: -
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NAD+ + [carbamoyl phosphate synthase 1]-N6-acetyl-L-lysine + H2O
nicotinamide + [carbamoyl phosphate synthase 1]-L-lysine + 2'-O-acetyl-ADP-ribose
Substrates: SIRT5 deacetylates carbamoyl phosphate synthetase 1 (CPS1), an enzyme which is the first and rate-limiting step of urea cycle
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NAD+ + [carbamoyl phosphate synthase 1]-N6-acetyl-L-lysine + H2O
nicotinamide + [carbamoyl phosphate synthase 1]-L-lysine + 2'-O-acetyl-ADP-ribose
Substrates: -
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NAD+ + [carbamoyl phosphate synthetase 1]-N6-acetyl-L-lysine + H2O
nicotinamide + [carbamoyl phosphate synthetase 1]-L-lysine + 2'-O-acetyl-ADP ribose
Substrates: SIRT5 plays a pivotal role in ammonia detoxification and disposal by activating carbamoyl phosphate synthetase 1 (CPS1) an enzyme, catalyzing the initial step of the urea cycle for ammonia detoxification and disposal. SIRT5 deacetylates CPS1 and up-regulates its activity. During fasting, NAD+ in liver mitochondria increases, thereby triggering SIRT5 deacetylation of CPS1 and adaptation to the increase in amino acid catabolism. Indeed, SIRT5 KO mice fail to up-regulate CPS1 activity and show elevated blood ammonia during fasting
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NAD+ + [carbamoyl phosphate synthetase 1]-N6-acetyl-L-lysine + H2O
nicotinamide + [carbamoyl phosphate synthetase 1]-L-lysine + 2'-O-acetyl-ADP ribose
Substrates: -
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NAD+ + [Cu/Zn superoxide dismutase]-N6-succinyl-L-lysine123 + H2O
nicotinamide + [Cu/Zn superoxide dismutase]-L-lysine123 + 2'-O-succinyl-ADP-ribose
Substrates: SIRT5 binds to, desuccinylates and activates the key antioxidant enzyme Cu/Zn superoxide dismutase (SOD1). SOD1-mediated reduction of reactive oxygen species (ROS) is increased when SIRT5 is co-expressed. Posttranslational regulation of SOD1 by means of succinylation and SIRT5-dependent desuccinylation is important for the growth of lung tumor cells
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NAD+ + [Cu/Zn superoxide dismutase]-N6-succinyl-L-lysine123 + H2O
nicotinamide + [Cu/Zn superoxide dismutase]-L-lysine123 + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [glutaminase]-N6-succinyl-L-lysine + H2O
nicotinamide + [glutaminase]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: SIRT5 desuccinylates glutaminase residue K164 to block ubiquitination of K158
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NAD+ + [glutaminase]-N6-succinyl-L-lysine + H2O
nicotinamide + [glutaminase]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: succinylation of glutaminase residue K164, no activity with K164R-GLS variant
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NAD+ + [histone H2B]-N6-succinyl-L-lysine9 + H2O
nicotinamide + [histone H2B]-L-lysine9 + 2'-O-succinyl-ADP-ribose
Substrates: partial desuccinylation
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NAD+ + [histone H2B]-N6-succinyl-L-lysine9 + H2O
nicotinamide + [histone H2B]-L-lysine9 + 2'-O-succinyl-ADP-ribose
Substrates: partial desuccinylation
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NAD+ + [N-hydroxyarylamine O-acetyltransferase]-N6-acetyl-L-lysine + H2O
nicotinamide + [N-hydroxyarylamine O-acetyltransferase]-L-lysine + 2'-O-acetyl-ADP-ribose
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Substrates: -
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NAD+ + [N-hydroxyarylamine O-acetyltransferase]-N6-acetyl-L-lysine + H2O
nicotinamide + [N-hydroxyarylamine O-acetyltransferase]-L-lysine + 2'-O-acetyl-ADP-ribose
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Substrates: -
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NAD+ + [protein]-N6-acetyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP-ribose
Substrates: the enzyme regulates protein function in diverse and often essential cellular processes, most notably translation
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NAD+ + [protein]-N6-acetyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP-ribose
Substrates: the enzyme can deacetylate acetyllysine independently whether the acetyl donor is acetyl-Coenzyme A or acetyl phosphate. Linear sequences alone are inadequate to predict CobB substrates and that structural analyses are necessary. CobB substrate acetyllyines appear to be located near the surface of the protein on a
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NAD+ + [protein]-N6-acetyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP-ribose
Substrates: weak deacetylase activity
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NAD+ + [protein]-N6-malonyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-malonyl-ADP-ribose
Substrates: -
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NAD+ + [protein]-N6-malonyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-malonyl-ADP-ribose
Substrates: -
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NAD+ + [protein]-N6-succinyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [protein]-N6-succinyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [protein]-N6-succinyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: protein lysine succinylation may represent a posttranslational modification that can be reversed by Sirt5 in vivo. Lysine succinylation occurs on several mammalian proteins
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NAD+ + [protein]-N6-succinyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: strong succinylase activity
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NAD+ + [protein]-N6-succinyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [protein]-N6-succinyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
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Substrates: -
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NAD+ + [protein]-N6-succinyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [protein]-N6-succinyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [PrpE protein]-N6-propionyl-L-lysine + H2O
nicotinamide + [PrpE protein]-L-lysine + 2'-O-propionyl-ADP-ribose
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Substrates: N-Lysine propionylation controls the activity of propionyl-CoA synthetase
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NAD+ + [PrpE protein]-N6-propionyl-L-lysine + H2O
nicotinamide + [PrpE protein]-L-lysine + 2'-O-propionyl-ADP-ribose
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Substrates: -
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NAD+ + [pyruvate dehydrogenase complex]-N6-succinyl-L-lysine + H2O
nicotinamide + [pyruvate dehydrogenase complex]-L-lysine + O-succinyl-ADP-ribose
Substrates: SIRT5 represses biochemical activity of, and cellular respiration through, the protein complex
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NAD+ + [pyruvate dehydrogenase complex]-N6-succinyl-L-lysine + H2O
nicotinamide + [pyruvate dehydrogenase complex]-L-lysine + O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [pyruvate kinase M2]-N6-succinyl-L-lysine311 + H2O
nicotinamide + [pyruvate kinase M2]-L-lysine311 + 2'-O-succinyl-ADP-ribose
Substrates: SIRT5 desuccinylates and activates PKM2
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NAD+ + [pyruvate kinase M2]-N6-succinyl-L-lysine311 + H2O
nicotinamide + [pyruvate kinase M2]-L-lysine311 + 2'-O-succinyl-ADP-ribose
Substrates: SIRT5 also desuccinylates recombinant Flag-tagged PKM2 substrate, but does not but affect its malonylation and glutarylation. The K311E mutation and K311E/K498E double mutation of PKM2 both increase the succinylation level of PKM2 by about 25%, while mutations K62R/E, K135R/E, and K498R/E have no significant effect
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NAD+ + [RcsB protein]-N6-acetyl-L-lysine180 + H2O
nicotinamide + [RcsB protein]-L-lysine180 + 2'-O-acetyl-ADP-ribose
Substrates: reversible Nepsilon-Lys acetylation of transcription factors is a mode of regulation of gene expression used by all cells
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NAD+ + [RcsB protein]-N6-acetyl-L-lysine180 + H2O
nicotinamide + [RcsB protein]-L-lysine180 + 2'-O-acetyl-ADP-ribose
-
Substrates: acetylation of the response regulator RcsB controls transcription from the small RNA promoter rprA
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NAD+ + [RcsB protein]-N6-acetyl-L-lysine180 + H2O
nicotinamide + [RcsB protein]-L-lysine180 + 2'-O-acetyl-ADP-ribose
Substrates: -
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NAD+ + [RcsB protein]-N6-acetyl-L-lysine180 + H2O
nicotinamide + [RcsB protein]-L-lysine180 + 2'-O-acetyl-ADP-ribose
-
Substrates: -
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NAD+ + [response regulator CheY]-N6-acetyl-L-lysine + H2O
nicotinamide + [response regulator CheY]-L-lysine + 2'-O-acetyl-ADP-ribose
-
Substrates: the enzyme regulates chemotaxis of Escherichia coli by deacetylating CheY
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NAD+ + [response regulator CheY]-N6-acetyl-L-lysine + H2O
nicotinamide + [response regulator CheY]-L-lysine + 2'-O-acetyl-ADP-ribose
-
Substrates: -
Products: -
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NAD+ + [response regulator CheY]-N6-acetyl-L-lysine + H2O
nicotinamide + [response regulator CheY]-L-lysine + 2'-O-acetyl-ADP-ribose
Escherichia coli W3110 / ATCC 27325
-
Substrates: the enzyme regulates chemotaxis of Escherichia coli by deacetylating CheY
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NAD+ + [response regulator CheY]-N6-acetyl-L-lysine + H2O
nicotinamide + [response regulator CheY]-L-lysine + 2'-O-acetyl-ADP-ribose
Escherichia coli W3110 / ATCC 27325
-
Substrates: -
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NAD+ + [succinate dehydrogenase]-N6-succinyl-L-lysine + H2O
nicotinamide + [succinate dehydrogenase]-L-lysine + O-succinyl-ADP-ribose
Substrates: SIRT5 represses biochemical activity of, and cellular respiration through, the protein complex
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NAD+ + [succinate dehydrogenase]-N6-succinyl-L-lysine + H2O
nicotinamide + [succinate dehydrogenase]-L-lysine + O-succinyl-ADP-ribose
Substrates: -
Products: -
Products: -
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NAD+ + [urate oxidase]-N6-acetyl-L-lysine + H2O
nicotinamide + [urate oxidase]-L-lysine + 2'-O-acetyl-ADP-ribose
Substrates: SIRT5 activates urate oxidase through deacetylation in mouse liver mitochondria
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NAD+ + [urate oxidase]-N6-acetyl-L-lysine + H2O
nicotinamide + [urate oxidase]-L-lysine + 2'-O-acetyl-ADP-ribose
Substrates: -
Products: -
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?
[2-oxoglutarate dehydrogenase]-N6-succinyl-L-lysine + NAD+ + H2O
[2-oxoglutarate dehydrogenase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5-mediated desuccinylation of 2-oxoglutarate dehydrogenase (OGDH) inhibits the OGDH complex's activity, leading to reduced mitochondrial membrane potential, decreased ATP production, increased ROS levels, and altered NADP/NADPH ratios, ultimately suppressing gastric cancer progression
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[2-oxoglutarate dehydrogenase]-N6-succinyl-L-lysine + NAD+ + H2O
[2-oxoglutarate dehydrogenase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[acyl-CoA oxidase 1]-N6-succinyl-L-lysine + NAD+ + H2O
[acyl-CoA oxidase 1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 can inhibit acyl-CoA oxidase 1 through desuccinylation, thereby reducing H2O2 levels and mitigating oxidative stress
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[acyl-CoA oxidase 1]-N6-succinyl-L-lysine + NAD+ + H2O
[acyl-CoA oxidase 1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
Products: -
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[c-myc]-N6-succinyl-L-lysine + NAD+ + H2O
[c-myc]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 promotes malignant advancement of chordoma by regulating the desuccinylation of c-myc
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[c-myc]-N6-succinyl-L-lysine + NAD+ + H2O
[c-myc]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[c-myc]-N6-succinyl-L-lysine + NAD+ + H2O
[c-myc]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 promotes malignant advancement of chordoma by regulating the desuccinylation of c-myc
Products: -
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[c-myc]-N6-succinyl-L-lysine + NAD+ + H2O
[c-myc]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[enhanced trifunctional enzyme subunit-alpha]-N6-succinyl-L-lysine + NAD+ + H2O
[enhanced trifunctional enzyme subunit-alpha]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 mediates desuccinylation at the Lys540, thereby increasing activity of enhanced trifunctional enzyme subunit-alpha (ECHA)
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[enhanced trifunctional enzyme subunit-alpha]-N6-succinyl-L-lysine + NAD+ + H2O
[enhanced trifunctional enzyme subunit-alpha]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 mediates desuccinylation at the Lys540
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[enhanced trifunctional enzyme subunit-alpha]-N6-succinyl-L-lysine + NAD+ + H2O
[enhanced trifunctional enzyme subunit-alpha]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 mediates desuccinylation at the Lys540, thereby increasing activity of enhanced trifunctional enzyme subunit-alpha (ECHA)
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[enhanced trifunctional enzyme subunit-alpha]-N6-succinyl-L-lysine + NAD+ + H2O
[enhanced trifunctional enzyme subunit-alpha]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 mediates desuccinylation at the Lys540
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[glucose-6-phosphate isomerase]-N6-succinyl-L-lysine + NAD+ + H2O
[glucose-6-phosphate isomerase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[glucose-6-phosphate isomerase]-N6-succinyl-L-lysine + NAD+ + H2O
[glucose-6-phosphate isomerase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[glutathione peroxidase Hyr1]-N6-succinyl-L-lysine + NAD+ + H2O
[glutathione peroxidase Hyr1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
-
Substrates: Sirt5 desuccinylates glutathione peroxidase Hyr1 to activate its enzyme activity, likely by affecting proper folding
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[glutathione peroxidase Hyr1]-N6-succinyl-L-lysine + NAD+ + H2O
[glutathione peroxidase Hyr1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
-
Substrates: -
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[inosine-5'-monophosphate dehydrogenase]-N6-succinyl-L-lysine + NAD+ + H2O
[inosine-5'-monophosphate dehydrogenase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 can directly interact with IMPDH1 and promotes desuccinylation on the N terminal of IMPDH1, thereby leading to increased IMPDH enzymatic activity, enhanced purine biosynthesis and promoted tumor cell proliferation
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[inosine-5'-monophosphate dehydrogenase]-N6-succinyl-L-lysine + NAD+ + H2O
[inosine-5'-monophosphate dehydrogenase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 promotes desuccinylation on the N terminal of IMPDH1
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[lactate dehydrogenase A]-N6-succinyl-L-lysine + NAD+ + H2O
[lactate dehydrogenase A]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[lactate dehydrogenase A]-N6-succinyl-L-lysine + NAD+ + H2O
[lactate dehydrogenase A]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: desuccinylation of Lys118
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[mitochondrial antiviral signaling protein]-N6-succinyl-L-lysine + NAD+ + H2O
[mitochondrial antiviral signaling protein]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5
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[mitochondrial antiviral signaling protein]-N6-succinyl-L-lysine + NAD+ + H2O
[mitochondrial antiviral signaling protein]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 mediates desuccinylation of mitochondrial antiviral signaling protein at Lys7
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[mitochondrial glutaminase]-N6-succinyl-L-lysine + NAD+ + H2O
[mitochondrial glutaminase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[mitochondrial glutaminase]-N6-succinyl-L-lysine + NAD+ + H2O
[mitochondrial glutaminase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[p53]-N6-succinyl-L-lysine + NAD+ + H2O
[p53]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: p53 desuccinylation results in its inhibition and the consequent suppression of both the expression of p53 target genes and p53-induced apoptosis
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[p53]-N6-succinyl-L-lysine + NAD+ + H2O
[p53]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
Products: -
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?
[p53]-N6-succinyl-L-lysine + NAD+ + H2O
[p53]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: p53 desuccinylation results in its inhibition and the consequent suppression of both the expression of p53 target genes and p53-induced apoptosis
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[p53]-N6-succinyl-L-lysine + NAD+ + H2O
[p53]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
Products: -
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?
[PKM2]-N6-succinyl-L-lysine + NAD+ + H2O
[PKM2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: desuccinylation of PKM2 at Lys311
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[PKM2]-N6-succinyl-L-lysine + NAD+ + H2O
[PKM2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: desuccinylation of PKM2 at Lys311
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[serine hydroxymethyltransferase 2]-N6-succinyl-L-lysine + NAD+ + H2O
[serine hydroxymethyltransferase 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: desuccinylation at Lys280 activates the catabolizing enzyme serine hydroxymethyltransferase 2 (SHMT2), which in turn promotes tumor progression in osteosarcoma U2OS and colorectal carcinoma (CRC) HCT116 cells
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[serine hydroxymethyltransferase 2]-N6-succinyl-L-lysine + NAD+ + H2O
[serine hydroxymethyltransferase 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: desuccinylation at Lys280
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[serine hydroxymethyltransferase 2]-N6-succinyl-L-lysine + NAD+ + H2O
[serine hydroxymethyltransferase 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: desuccinylation at Lys280 activates the catabolizing enzyme serine hydroxymethyltransferase 2 (SHMT2), which in turn promotes tumor progression in osteosarcoma U2OS and colorectal carcinoma (CRC) HCT116 cells
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[serine hydroxymethyltransferase 2]-N6-succinyl-L-lysine + NAD+ + H2O
[serine hydroxymethyltransferase 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: desuccinylation at Lys280
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[succinate dehydrogenase complex subunit A]-N6-succinyl-L-lysine + NAD+ + H2O
[succinate dehydrogenase complex subunit A]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: desuccinylation of succinate dehydrogenase complex subunit A and the inhibition of its enzymatic activity lead to higher levels of succinate, which determines TrxR2 activation. Through this mechanism, SIRT5 protects tumor cells from oxidative damage and promotes their proliferation
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[succinate dehydrogenase complex subunit A]-N6-succinyl-L-lysine + NAD+ + H2O
[succinate dehydrogenase complex subunit A]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
Products: -
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[succinate dehydrogenase complex subunit A]-N6-succinyl-L-lysine + NAD+ + H2O
[succinate dehydrogenase complex subunit A]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: desuccinylation of succinate dehydrogenase complex subunit A and the inhibition of its enzymatic activity lead to higher levels of succinate, which determines TrxR2 activation. Through this mechanism, SIRT5 protects tumor cells from oxidative damage and promotes their proliferation
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[succinate dehydrogenase complex subunit A]-N6-succinyl-L-lysine + NAD+ + H2O
[succinate dehydrogenase complex subunit A]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
Products: -
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[superoxide dismutase 1]-N6-succinyl-L-lysine + NAD+ + H2O
[superoxide dismutase 1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
Products: -
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[superoxide dismutase 1]-N6-succinyl-L-lysine + NAD+ + H2O
[superoxide dismutase 1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
Products: -
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[TBK1]-N6-succinyl-L-lysine + NAD+ + H2O
[TBK1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: desuccinylation of TBK1 by SIRT5 enhances TBK1 kinase activity, enhances the interaction of TBK1 with IRF3 or TRAF2 and regulates inflammatory response of macrophages in sepsis
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[TBK1]-N6-succinyl-L-lysine + NAD+ + H2O
[TBK1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
Products: -
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[thioredoxin Trx2]-N6-succinyl-L-lysine + NAD+ + H2O
[thioredoxin Trx2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
-
Substrates: Sirt5 desuccinylates thioredoxin Trx2 to activate its enzyme activity, likely by affecting proper folding
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[thioredoxin Trx2]-N6-succinyl-L-lysine + NAD+ + H2O
[thioredoxin Trx2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
-
Substrates: -
Products: -
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[ubiquinol-cytochrome C reductase core protein 2]-N6-succinyl-L-lysine + NAD+ + H2O
[ubiquinol-cytochrome C reductase core protein 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 -mediated desuccinylation of UQCRC2 attenuates osteogenic differentiation of aged BM-MSCs through impairing mitochondrial homeostasis
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[ubiquinol-cytochrome C reductase core protein 2]-N6-succinyl-L-lysine + NAD+ + H2O
[ubiquinol-cytochrome C reductase core protein 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: desuccinylation of Lys250
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additional information
?
-
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Substrates: it is proposed that YfiQ and CobB catalyze the reversible acetylation of a protein that mediates carbon-induced cpxP transcription
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additional information
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-
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Substrates: the enzyme shows dual enzymatic activities to catalyze the removal of two structurally different lysine acyl groups, acetyl and succinyl, from the modified lysine residues
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additional information
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-
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Substrates: global identification of CobB substrates using an Escherichia coli proteome microarray
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additional information
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-
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Substrates: global identification of CobB substrates using an Escherichia coli proteome microarray
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additional information
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Substrates: catalytic efficiency (kcat/Km) of Sirt5 with the histone H3K9 acetyl peptide is about 500fold lower than that of Sirt1. Sirtuin 5 has only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr102 and Arg105) that bind to malonylated and succinylated substrates and define the specificity
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additional information
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Substrates: Sirt5 does not deacetylate glutamate dehydrogenase or isocitrate dehydrogenase 2
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additional information
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-
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Substrates: Sirt5 does not deacetylate glutamate dehydrogenase or isocitrate dehydrogenase 2
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additional information
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Substrates: no activity with Ac-Leu-Gly-(N6-acetyl)Lys-7-amido-4-methylcoumarin
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additional information
?
-
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Substrates: no activity with Ac-Leu-Gly-(N6-acetyl)Lys-7-amido-4-methylcoumarin
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additional information
?
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Substrates: SIRT5 electrostatically binds to cardiolipin and desuccinylates mitochondrial inner membrane proteins including multiple subunits of all four electron transport chain (ETC) complexes and ATP synthase. SIRT5 targets lysines at the protein-lipid interface of Complex II. Mass spectrometry identifies 14 SIRT5 target sites on the SDHA subunit of Complex II and another eight on SDHB. Molecular modeling reveals that six of the eight SIRT5 target sites on SDHB orient toward the predicted membrane interface where SDHB interacts with SDHC/SDHD
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additional information
?
-
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Substrates: SIRT5 electrostatically binds to cardiolipin and desuccinylates mitochondrial inner membrane proteins including multiple subunits of all four electron transport chain (ETC) complexes and ATP synthase. SIRT5 targets lysines at the protein-lipid interface of Complex II. Mass spectrometry identifies 14 SIRT5 target sites on the SDHA subunit of Complex II and another eight on SDHB. Molecular modeling reveals that six of the eight SIRT5 target sites on SDHB orient toward the predicted membrane interface where SDHB interacts with SDHC/SDHD
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additional information
?
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Substrates: Sirt5 catalyzes the desuccinylation of histone peptides, molecular mechanism, overview. Human Sirt5 is a ubiquitous desuccinylase that catalyzes the desuccinylation of diverse histone succinyl sites with sequence selectivity. Among the 13 identified sites, H2BK116su is the most favorable Sirt5 substrate, with H4K12su showing the lowest catalytic efficiency and no activity observed in the presence of H4K31su
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additional information
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Substrates: Sirt5 catalyzes the desuccinylation of histone peptides, molecular mechanism, overview. Human Sirt5 is a ubiquitous desuccinylase that catalyzes the desuccinylation of diverse histone succinyl sites with sequence selectivity. Among the 13 identified sites, H2BK116su is the most favorable Sirt5 substrate, with H4K12su showing the lowest catalytic efficiency and no activity observed in the presence of H4K31su
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additional information
?
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Substrates: SIRT5 catalyzes the removal of negatively charged lysine acyl modifications: succinyl, malonyl, and glutaryl groups. SIRT5 is selective only for 3-5 carbon chains acidic acyl modifications, and displays no detectable activity against either an acetyl modification, a neutral 2 carbon group, or an adipoyl, a 6-carbon acidic modification
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additional information
?
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Substrates: enzyme activity assay method, overview
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additional information
?
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Substrates: synthsis of substrate peptide (2-Abz)-GVLK (succ)A [Y (3-NO2)]GV-NH2
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additional information
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Substrates: synthsis of substrate peptide (2-Abz)-GVLK (succ)A [Y (3-NO2)]GV-NH2
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additional information
?
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Substrates: essential role for the conserved main chain hydrogen bonds formed by the succinyl lysine (0), +1, and +3 sites for substrate-enzyme recognition. A proline residue at the +1 site of the histone succinylation substrate is unfavorable for Sirt5 interaction. Molecular mechanism underlying the sequence-selective desuccinylase activity of Sirt5, overview. No activity with H4K31su, and mutant substrates H3K9(4-15)-S10Psu and H3K56(51-62)-S57Psu. Usage of peptides of histone substrates
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additional information
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Substrates: essential role for the conserved main chain hydrogen bonds formed by the succinyl lysine (0), +1, and +3 sites for substrate-enzyme recognition. A proline residue at the +1 site of the histone succinylation substrate is unfavorable for Sirt5 interaction. Molecular mechanism underlying the sequence-selective desuccinylase activity of Sirt5, overview. No activity with H4K31su, and mutant substrates H3K9(4-15)-S10Psu and H3K56(51-62)-S57Psu. Usage of peptides of histone substrates
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additional information
?
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Substrates: the enzyme shows low deacetylation activity but significant desuccinylation, demalonylation and deglutarylation activities
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additional information
?
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Substrates: SIRT5 has the highest catalytic efficiency for deglutarylation, followed by desuccinylation and demalonylation and low deacetylation activity
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additional information
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Substrates: Sirt5 shows negligible activity toward lysine deacetylation
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additional information
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Substrates: SIRT5 modifies lysine succinylation, malonylation, and glutarylation
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additional information
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Substrates: three-dimensional modeling of Complex II suggests that several SIRT5-targeted lysine residues lie at the protein-lipid interface of succinate dehydrogenase subunit B. Succinylation at these sites may disrupt Complex II subunit-subunit interactions and electron transfer. SIRT5 electrostatically binds to cardiolipin and desuccinylates mitochondrial inner membrane proteins including multiple subunits of all four electron transport chain (ETC) complexes and ATP synthase. SIRT5 targets lysines at the protein-lipid interface of Complex II
Products: -
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additional information
?
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Substrates: three-dimensional modeling of Complex II suggests that several SIRT5-targeted lysine residues lie at the protein-lipid interface of succinate dehydrogenase subunit B. Succinylation at these sites may disrupt Complex II subunit-subunit interactions and electron transfer. SIRT5 electrostatically binds to cardiolipin and desuccinylates mitochondrial inner membrane proteins including multiple subunits of all four electron transport chain (ETC) complexes and ATP synthase. SIRT5 targets lysines at the protein-lipid interface of Complex II
Products: -
Products: -
?
additional information
?
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Substrates: SIRT5 catalyzes the removal of negatively charged lysine acyl modifications: succinyl, malonyl, and glutaryl groups. SIRT5 is selective only for 3-5 carbon chains acidic acyl modifications, and displays no detectable activity against either an acetyl modification, a neutral 2 carbon group, or an adipoyl, a 6-carbon acidic modification
Products: -
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additional information
?
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Substrates: protein malonylation and succinylation lysine sites are identified by immunoprecipitation coupled lipid chromatography-tandem mass spectrometry (LC-MS/MS) methods
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additional information
?
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Substrates: protein malonylation and succinylation lysine sites are identified by immunoprecipitation coupled lipid chromatography-tandem mass spectrometry (LC-MS/MS) methods
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additional information
?
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Substrates: SIRT5 has the highest catalytic efficiency for deglutarylation, followed by desuccinylation and demalonylation and low deacetylation activity
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additional information
?
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Substrates: protein malonylation and succinylation lysine sites are identified by immunoprecipitation coupled lipid chromatography-tandem mass spectrometry (LC-MS/MS) methods
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Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
CH3CONH-AR-[Nepsilon-succinyl-lysine]-ST-CONH2 + NAD+ + H2O
CH3CONH-ARKST-CONH2 + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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?
NAD+ + [acetyl-coenzyme A synthetase]-N6-acetyl-L-lysine609 + H2O
nicotinamide + [acetyl-coenzyme A synthetase]-L-lysine609 + 2'-O-acetyl-ADP-ribose
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Substrates: deacetylation by CobB activates the acetyl-coenzyme A synthetase
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?
NAD+ + [ATP synthase]-N6-succinyl-L-lysine + H2O
nicotinamide + [ATP synthase]-L-lysine + 2'-O-succinyl-ADP-ribose
NAD+ + [carbamoyl phosphate synthase 1]-N6-acetyl-L-lysine + H2O
nicotinamide + [carbamoyl phosphate synthase 1]-L-lysine + 2'-O-acetyl-ADP ribose
Substrates: SIRT5 deacetylates carbamoyl phosphate synthetase 1 (CPS1), an enzyme which is the first and rate-limiting step of urea cycle. Deacetylation of CPS1 by SIRT5 results in activation of CPS1 enzymatic activity
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NAD+ + [carbamoyl phosphate synthase 1]-N6-acetyl-L-lysine + H2O
nicotinamide + [carbamoyl phosphate synthase 1]-L-lysine + 2'-O-acetyl-ADP-ribose
Substrates: SIRT5 deacetylates carbamoyl phosphate synthetase 1 (CPS1), an enzyme which is the first and rate-limiting step of urea cycle
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NAD+ + [carbamoyl phosphate synthase 1]-N6-succinyl-L-lysine + H2O
nicotinamide + [carbamoyl phosphate synthase 1]-L-lysine + 2'-O-succinyl-ADP ribose
Substrates: deletion of Sirt5 in mice increases the level of succinylation on carbamoyl phosphate synthase 1
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NAD+ + [carbamoyl phosphate synthetase 1]-N6-acetyl-L-lysine + H2O
nicotinamide + [carbamoyl phosphate synthetase 1]-L-lysine + 2'-O-acetyl-ADP ribose
Substrates: SIRT5 plays a pivotal role in ammonia detoxification and disposal by activating carbamoyl phosphate synthetase 1 (CPS1) an enzyme, catalyzing the initial step of the urea cycle for ammonia detoxification and disposal. SIRT5 deacetylates CPS1 and up-regulates its activity. During fasting, NAD+ in liver mitochondria increases, thereby triggering SIRT5 deacetylation of CPS1 and adaptation to the increase in amino acid catabolism. Indeed, SIRT5 KO mice fail to up-regulate CPS1 activity and show elevated blood ammonia during fasting
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NAD+ + [carbamoyl phosphate synthetase 1]-N6-glutaryl-L-lysine + H2O
nicotinamide + [carbamoyl phosphate synthetase 1]-L-lysine + 2'-O-glutaryl-ADP-ribose
Substrates: -
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NAD+ + [Cu/Zn superoxide dismutase]-N6-succinyl-L-lysine123 + H2O
nicotinamide + [Cu/Zn superoxide dismutase]-L-lysine123 + 2'-O-succinyl-ADP-ribose
Substrates: SIRT5 binds to, desuccinylates and activates the key antioxidant enzyme Cu/Zn superoxide dismutase (SOD1). SOD1-mediated reduction of reactive oxygen species (ROS) is increased when SIRT5 is co-expressed. Posttranslational regulation of SOD1 by means of succinylation and SIRT5-dependent desuccinylation is important for the growth of lung tumor cells
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NAD+ + [forkhead box O3]-N6-acetyl-L-lysine + H2O
nicotinamide + [forkhead box O3]-L-lysine + 2'-O-acetyl-ADP-ribose
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Substrates: the enzyme deacetylates FOXO3 at K271 and K290
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NAD+ + [glucose 6-phosphate dehydrogenase]-N6-succinyl-L-lysine + H2O
nicotinamide + [glucose 6-phosphate dehydrogenase]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [glucose-6-phosphate dehydrogenase]-N6-acetyl-L-lysine + H2O
nicotinamide + [glucose-6-phosphate dehydrogenase]-L-lysine + 2'-O-acetyl-ADP-ribose
-
Substrates: -
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NAD+ + [glutaminase]-N6-succinyl-L-lysine + H2O
nicotinamide + [glutaminase]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: SIRT5 desuccinylates glutaminase residue K164 to block ubiquitination of K158
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NAD+ + [histone H2B]-N6-succinyl-L-lysine9 + H2O
nicotinamide + [histone H2B]-L-lysine9 + 2'-O-succinyl-ADP-ribose
Substrates: partial desuccinylation
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NAD+ + [histone H4]-N6-acetyl-L-lysine16 + H2O
nicotinamide + [histone H4]-L-lysine16 + 2'-O-acetyl-ADP-ribose
Substrates: deacetylation, cf. EC 2.3.1.286
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NAD+ + [IDH2]-N6-succinyl-L-lysine + H2O
nicotinamide + [IDH2]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: i.e. isocitrate dehydrogenase [NADP+]
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NAD+ + [isocitrate dehydrogenase 2]-N6-acetyl-L-lysine + H2O
nicotinamide + [isocitrate dehydrogenase 2]-L-lysine + 2'-O-acetyl-ADP-ribose
-
Substrates: -
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NAD+ + [N-hydroxyarylamine O-acetyltransferase]-N6-acetyl-L-lysine + H2O
nicotinamide + [N-hydroxyarylamine O-acetyltransferase]-L-lysine + 2'-O-acetyl-ADP-ribose
NAD+ + [protein]-N6-acetyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP-ribose
NAD+ + [protein]-N6-malonyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-malonyl-ADP-ribose
NAD+ + [protein]-N6-succinyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
NAD+ + [PrpE protein]-N6-propionyl-L-lysine + H2O
nicotinamide + [PrpE protein]-L-lysine + 2'-O-propionyl-ADP-ribose
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Substrates: N-Lysine propionylation controls the activity of propionyl-CoA synthetase
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NAD+ + [pyruvate dehydrogenase complex]-N6-succinyl-L-lysine + H2O
nicotinamide + [pyruvate dehydrogenase complex]-L-lysine + O-succinyl-ADP-ribose
Substrates: SIRT5 represses biochemical activity of, and cellular respiration through, the protein complex
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NAD+ + [pyruvate kinase M2]-N6-succinyl-L-lysine311 + H2O
nicotinamide + [pyruvate kinase M2]-L-lysine311 + 2'-O-succinyl-ADP-ribose
Substrates: SIRT5 desuccinylates and activates PKM2
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NAD+ + [RcsB protein]-N6-acetyl-L-lysine180 + H2O
nicotinamide + [RcsB protein]-L-lysine180 + 2'-O-acetyl-ADP-ribose
NAD+ + [response regulator CheY]-N6-acetyl-L-lysine + H2O
nicotinamide + [response regulator CheY]-L-lysine + 2'-O-acetyl-ADP-ribose
NAD+ + [succinate dehydrogenase]-N6-succinyl-L-lysine + H2O
nicotinamide + [succinate dehydrogenase]-L-lysine + O-succinyl-ADP-ribose
Substrates: SIRT5 represses biochemical activity of, and cellular respiration through, the protein complex
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NAD+ + [urate oxidase]-N6-acetyl-L-lysine + H2O
nicotinamide + [urate oxidase]-L-lysine + 2'-O-acetyl-ADP-ribose
Substrates: SIRT5 activates urate oxidase through deacetylation in mouse liver mitochondria
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[2-oxoglutarate dehydrogenase]-N6-succinyl-L-lysine + NAD+ + H2O
[2-oxoglutarate dehydrogenase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5-mediated desuccinylation of 2-oxoglutarate dehydrogenase (OGDH) inhibits the OGDH complex's activity, leading to reduced mitochondrial membrane potential, decreased ATP production, increased ROS levels, and altered NADP/NADPH ratios, ultimately suppressing gastric cancer progression
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[acyl-CoA oxidase 1]-N6-succinyl-L-lysine + NAD+ + H2O
[acyl-CoA oxidase 1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 can inhibit acyl-CoA oxidase 1 through desuccinylation, thereby reducing H2O2 levels and mitigating oxidative stress
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[c-myc]-N6-succinyl-L-lysine + NAD+ + H2O
[c-myc]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[enhanced trifunctional enzyme subunit-alpha]-N6-succinyl-L-lysine + NAD+ + H2O
[enhanced trifunctional enzyme subunit-alpha]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[glucose-6-phosphate isomerase]-N6-succinyl-L-lysine + NAD+ + H2O
[glucose-6-phosphate isomerase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[glutaminase]-N6-succinyl-L-lysine + NAD+ + H2O
[glutaminase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[glutathione peroxidase Hyr1]-N6-succinyl-L-lysine + NAD+ + H2O
[glutathione peroxidase Hyr1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
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Substrates: Sirt5 desuccinylates glutathione peroxidase Hyr1 to activate its enzyme activity, likely by affecting proper folding
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[histidine triad nucleotide binding protein 1]-N6-succinyl-L-lysine + NAD+ + H2O
[histidine triad nucleotide binding protein 1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[inosine-5'-monophosphate dehydrogenase]-N6-succinyl-L-lysine + NAD+ + H2O
[inosine-5'-monophosphate dehydrogenase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 can directly interact with IMPDH1 and promotes desuccinylation on the N terminal of IMPDH1, thereby leading to increased IMPDH enzymatic activity, enhanced purine biosynthesis and promoted tumor cell proliferation
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[isocitrate dehydrogenase 2]-N6-acetyl-L-lysine + NAD+ + H2O
[isocitrate dehydrogenase 2]-L-lysine + 2''-O-acetyl-ADP-D-ribose + nicotinamide
Substrates: -
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[lactate dehydrogenase A]-N6-succinyl-L-lysine + NAD+ + H2O
[lactate dehydrogenase A]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[mitochondrial antiviral signaling protein]-N6-succinyl-L-lysine + NAD+ + H2O
[mitochondrial antiviral signaling protein]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5
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[mitochondrial malic enzyme 2]-N6-succinyl-L-lysine + NAD+ + H2O
[mitochondrial malic enzyme 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[p53]-N6-succinyl-L-lysine + NAD+ + H2O
[p53]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[serine hydroxymethyltransferase 2]-N6-succinyl-L-lysine + NAD+ + H2O
[serine hydroxymethyltransferase 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[succinate dehydrogenase complex subunit A]-N6-succinyl-L-lysine + NAD+ + H2O
[succinate dehydrogenase complex subunit A]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
[superoxide dismutase 1]-N6-acetyl-L-lysine + NAD+ + H2O
[superoxide dismutase 1]-L-lysine + 2''-O-acetyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 desuccinylates and activates SOD1, thereby exerting a key function in ROS detoxification
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[superoxide dismutase 1]-N6-succinal-L-lysine + NAD+ + H2O
[superoxide dismutase 1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 desuccinylates and activates SOD1, thereby exerting a key function in ROS detoxification
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[TBK1]-N6-succinyl-L-lysine + NAD+ + H2O
[TBK1]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: desuccinylation of TBK1 by SIRT5 enhances TBK1 kinase activity, enhances the interaction of TBK1 with IRF3 or TRAF2 and regulates inflammatory response of macrophages in sepsis
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[thioredoxin Trx2]-N6-succinyl-L-lysine + NAD+ + H2O
[thioredoxin Trx2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
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Substrates: Sirt5 desuccinylates thioredoxin Trx2 to activate its enzyme activity, likely by affecting proper folding
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[ubiquinol-cytochrome C reductase core protein 2]-N6-succinyl-L-lysine + NAD+ + H2O
[ubiquinol-cytochrome C reductase core protein 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 -mediated desuccinylation of UQCRC2 attenuates osteogenic differentiation of aged BM-MSCs through impairing mitochondrial homeostasis
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NAD+ + [ATP synthase]-N6-succinyl-L-lysine + H2O
nicotinamide + [ATP synthase]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [ATP synthase]-N6-succinyl-L-lysine + H2O
nicotinamide + [ATP synthase]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [N-hydroxyarylamine O-acetyltransferase]-N6-acetyl-L-lysine + H2O
nicotinamide + [N-hydroxyarylamine O-acetyltransferase]-L-lysine + 2'-O-acetyl-ADP-ribose
-
Substrates: -
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NAD+ + [N-hydroxyarylamine O-acetyltransferase]-N6-acetyl-L-lysine + H2O
nicotinamide + [N-hydroxyarylamine O-acetyltransferase]-L-lysine + 2'-O-acetyl-ADP-ribose
-
Substrates: -
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NAD+ + [protein]-N6-acetyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP-ribose
Substrates: the enzyme regulates protein function in diverse and often essential cellular processes, most notably translation
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NAD+ + [protein]-N6-acetyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP-ribose
Substrates: weak deacetylase activity
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NAD+ + [protein]-N6-malonyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-malonyl-ADP-ribose
Substrates: -
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NAD+ + [protein]-N6-malonyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-malonyl-ADP-ribose
Substrates: -
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NAD+ + [protein]-N6-succinyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [protein]-N6-succinyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [protein]-N6-succinyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: protein lysine succinylation may represent a posttranslational modification that can be reversed by Sirt5 in vivo. Lysine succinylation occurs on several mammalian proteins
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NAD+ + [protein]-N6-succinyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: strong succinylase activity
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NAD+ + [protein]-N6-succinyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [protein]-N6-succinyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
-
Substrates: -
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NAD+ + [protein]-N6-succinyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [protein]-N6-succinyl-L-lysine + H2O
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
Substrates: -
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NAD+ + [RcsB protein]-N6-acetyl-L-lysine180 + H2O
nicotinamide + [RcsB protein]-L-lysine180 + 2'-O-acetyl-ADP-ribose
Substrates: reversible Nepsilon-Lys acetylation of transcription factors is a mode of regulation of gene expression used by all cells
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NAD+ + [RcsB protein]-N6-acetyl-L-lysine180 + H2O
nicotinamide + [RcsB protein]-L-lysine180 + 2'-O-acetyl-ADP-ribose
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Substrates: acetylation of the response regulator RcsB controls transcription from the small RNA promoter rprA
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NAD+ + [response regulator CheY]-N6-acetyl-L-lysine + H2O
nicotinamide + [response regulator CheY]-L-lysine + 2'-O-acetyl-ADP-ribose
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Substrates: the enzyme regulates chemotaxis of Escherichia coli by deacetylating CheY
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NAD+ + [response regulator CheY]-N6-acetyl-L-lysine + H2O
nicotinamide + [response regulator CheY]-L-lysine + 2'-O-acetyl-ADP-ribose
Escherichia coli W3110 / ATCC 27325
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Substrates: the enzyme regulates chemotaxis of Escherichia coli by deacetylating CheY
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[c-myc]-N6-succinyl-L-lysine + NAD+ + H2O
[c-myc]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 promotes malignant advancement of chordoma by regulating the desuccinylation of c-myc
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[c-myc]-N6-succinyl-L-lysine + NAD+ + H2O
[c-myc]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 promotes malignant advancement of chordoma by regulating the desuccinylation of c-myc
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[enhanced trifunctional enzyme subunit-alpha]-N6-succinyl-L-lysine + NAD+ + H2O
[enhanced trifunctional enzyme subunit-alpha]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 mediates desuccinylation at the Lys540, thereby increasing activity of enhanced trifunctional enzyme subunit-alpha (ECHA)
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[enhanced trifunctional enzyme subunit-alpha]-N6-succinyl-L-lysine + NAD+ + H2O
[enhanced trifunctional enzyme subunit-alpha]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: SIRT5 mediates desuccinylation at the Lys540, thereby increasing activity of enhanced trifunctional enzyme subunit-alpha (ECHA)
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[glucose-6-phosphate isomerase]-N6-succinyl-L-lysine + NAD+ + H2O
[glucose-6-phosphate isomerase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[glucose-6-phosphate isomerase]-N6-succinyl-L-lysine + NAD+ + H2O
[glucose-6-phosphate isomerase]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: -
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[p53]-N6-succinyl-L-lysine + NAD+ + H2O
[p53]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: p53 desuccinylation results in its inhibition and the consequent suppression of both the expression of p53 target genes and p53-induced apoptosis
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[p53]-N6-succinyl-L-lysine + NAD+ + H2O
[p53]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: p53 desuccinylation results in its inhibition and the consequent suppression of both the expression of p53 target genes and p53-induced apoptosis
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[serine hydroxymethyltransferase 2]-N6-succinyl-L-lysine + NAD+ + H2O
[serine hydroxymethyltransferase 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: desuccinylation at Lys280 activates the catabolizing enzyme serine hydroxymethyltransferase 2 (SHMT2), which in turn promotes tumor progression in osteosarcoma U2OS and colorectal carcinoma (CRC) HCT116 cells
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[serine hydroxymethyltransferase 2]-N6-succinyl-L-lysine + NAD+ + H2O
[serine hydroxymethyltransferase 2]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: desuccinylation at Lys280 activates the catabolizing enzyme serine hydroxymethyltransferase 2 (SHMT2), which in turn promotes tumor progression in osteosarcoma U2OS and colorectal carcinoma (CRC) HCT116 cells
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[succinate dehydrogenase complex subunit A]-N6-succinyl-L-lysine + NAD+ + H2O
[succinate dehydrogenase complex subunit A]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: desuccinylation of succinate dehydrogenase complex subunit A and the inhibition of its enzymatic activity lead to higher levels of succinate, which determines TrxR2 activation. Through this mechanism, SIRT5 protects tumor cells from oxidative damage and promotes their proliferation
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[succinate dehydrogenase complex subunit A]-N6-succinyl-L-lysine + NAD+ + H2O
[succinate dehydrogenase complex subunit A]-L-lysine + 2''-O-succinyl-ADP-D-ribose + nicotinamide
Substrates: desuccinylation of succinate dehydrogenase complex subunit A and the inhibition of its enzymatic activity lead to higher levels of succinate, which determines TrxR2 activation. Through this mechanism, SIRT5 protects tumor cells from oxidative damage and promotes their proliferation
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additional information
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Substrates: it is proposed that YfiQ and CobB catalyze the reversible acetylation of a protein that mediates carbon-induced cpxP transcription
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additional information
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Substrates: SIRT5 electrostatically binds to cardiolipin and desuccinylates mitochondrial inner membrane proteins including multiple subunits of all four electron transport chain (ETC) complexes and ATP synthase. SIRT5 targets lysines at the protein-lipid interface of Complex II. Mass spectrometry identifies 14 SIRT5 target sites on the SDHA subunit of Complex II and another eight on SDHB. Molecular modeling reveals that six of the eight SIRT5 target sites on SDHB orient toward the predicted membrane interface where SDHB interacts with SDHC/SDHD
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additional information
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Substrates: SIRT5 electrostatically binds to cardiolipin and desuccinylates mitochondrial inner membrane proteins including multiple subunits of all four electron transport chain (ETC) complexes and ATP synthase. SIRT5 targets lysines at the protein-lipid interface of Complex II. Mass spectrometry identifies 14 SIRT5 target sites on the SDHA subunit of Complex II and another eight on SDHB. Molecular modeling reveals that six of the eight SIRT5 target sites on SDHB orient toward the predicted membrane interface where SDHB interacts with SDHC/SDHD
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additional information
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Substrates: Sirt5 catalyzes the desuccinylation of histone peptides, molecular mechanism, overview. Human Sirt5 is a ubiquitous desuccinylase that catalyzes the desuccinylation of diverse histone succinyl sites with sequence selectivity. Among the 13 identified sites, H2BK116su is the most favorable Sirt5 substrate, with H4K12su showing the lowest catalytic efficiency and no activity observed in the presence of H4K31su
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additional information
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Substrates: Sirt5 catalyzes the desuccinylation of histone peptides, molecular mechanism, overview. Human Sirt5 is a ubiquitous desuccinylase that catalyzes the desuccinylation of diverse histone succinyl sites with sequence selectivity. Among the 13 identified sites, H2BK116su is the most favorable Sirt5 substrate, with H4K12su showing the lowest catalytic efficiency and no activity observed in the presence of H4K31su
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additional information
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Substrates: SIRT5 catalyzes the removal of negatively charged lysine acyl modifications: succinyl, malonyl, and glutaryl groups. SIRT5 is selective only for 3-5 carbon chains acidic acyl modifications, and displays no detectable activity against either an acetyl modification, a neutral 2 carbon group, or an adipoyl, a 6-carbon acidic modification
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additional information
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Substrates: SIRT5 modifies lysine succinylation, malonylation, and glutarylation
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additional information
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Substrates: three-dimensional modeling of Complex II suggests that several SIRT5-targeted lysine residues lie at the protein-lipid interface of succinate dehydrogenase subunit B. Succinylation at these sites may disrupt Complex II subunit-subunit interactions and electron transfer. SIRT5 electrostatically binds to cardiolipin and desuccinylates mitochondrial inner membrane proteins including multiple subunits of all four electron transport chain (ETC) complexes and ATP synthase. SIRT5 targets lysines at the protein-lipid interface of Complex II
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additional information
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Substrates: three-dimensional modeling of Complex II suggests that several SIRT5-targeted lysine residues lie at the protein-lipid interface of succinate dehydrogenase subunit B. Succinylation at these sites may disrupt Complex II subunit-subunit interactions and electron transfer. SIRT5 electrostatically binds to cardiolipin and desuccinylates mitochondrial inner membrane proteins including multiple subunits of all four electron transport chain (ETC) complexes and ATP synthase. SIRT5 targets lysines at the protein-lipid interface of Complex II
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additional information
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Substrates: SIRT5 catalyzes the removal of negatively charged lysine acyl modifications: succinyl, malonyl, and glutaryl groups. SIRT5 is selective only for 3-5 carbon chains acidic acyl modifications, and displays no detectable activity against either an acetyl modification, a neutral 2 carbon group, or an adipoyl, a 6-carbon acidic modification
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
the zinc-binding domain of the sirtuin proteins may play a similar role in substrate-specific recognition
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2S)-2-[(naphthalen-2-yl)sulfanyl]-4-oxo-4-[(3-phenylpropyl)amino]butanoic acid
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(2S)-4-[3-(methylcarbamoyl)anilino]-2-[(naphthalen-2-yl)sulfanyl]-4-oxobutanoic acid
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(2S)-4-[[(5S)-5-acetamido-6-amino-6-oxohexyl]amino]-2-[(naphthalen-2-yl)sulfanyl]-4-oxobutanoic acid
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(3E)-3-[(3,5-dibromo-4-hydroxyphenyl)methylidene]-5-iodo-1,3-dihydro-2H-indol-2-one
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(5E)-1-ethyl-5-(1H-indol-3-ylmethylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
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(5E)-5-(1H-indol-3-ylmethylidene)-1-methyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
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(5E)-5-[4-(benzyloxy)benzylidene]-1-(prop-2-en-1-yl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
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(5E)-5-[4-(benzyloxy)benzylidene]-1-ethyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
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(5E)-5-[4-(benzyloxy)benzylidene]-1-methyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
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(5E)-5-[[4-(benzyloxy)phenyl]methylidene]-1-(prop-2-en-1-yl)-2-sulfanylidene-1,3-diazinane-4,6-dione
(5E)-5-[[4-(benzyloxy)phenyl]methylidene]-1-methyl-2-sulfanylidene-1,3-diazinane-4,6-dione
(5E)-5-[[5-(2,3-dichlorophenyl)furan-2-yl]methylidene]-1-(prop-2-en-1-yl)-2-sulfanylidene-1,3-diazinane-4,6-dione
(5E)-5-[[5-(2,3-dichlorophenyl)furan-2-yl]methylidene]-1-(prop-2-en-1-yl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
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1-(2-(9H-pyrido[3,4-b]indol-9-yl)ethyl)-3-phenylurea
10% inhibition at 0.1 mM
2-cyano-3-[5-(4-cyanophenyl)furan-2-yl]-N-(3,4-dimethylphenyl)propanamide
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2-cyano-N-(3,4-dimethylphenyl)-3-[5-(4-nitrophenyl)furan-2-yl]propanamide
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3',5'-dimethyl-1'-phenyl-1H,1'H-[3,4'-bipyrazole]-5-carboxylic acid
21.54% inhibition at 0.1 mM
3-(((2-(9H-pyrido[3,4-b]indol-9-yl)ethyl)amino)methyl)benzoic acid
32% inhibition at 0.1 mM
3-((2-(9H-pyrido[3,4-b]indol-9-yl)acetamido)methyl)benzoic acid
21% inhibition at 0.1 mM
3-((2-(9H-pyrido[3,4-b]indol-9-yl)ethyl)carbamoyl)benzoicacid
15% inhibition at 0.1 mM
3-(3,5-dibromo-4-hydroxybenzyliden)-5-iodo-1,3-dihydroindol-2-one
i.e. GW5074, potent inhibitor for desuccinylation activity of Sirt5. 0.1 mM inhibitor reduces Sirt5 desuccinylation activity (substrate: SKEYFS-(succinylLys)-QK) to about 15%. Weaker effects in Sirt5 deacetylation assays. Deacetylation activity is reduced to about 30% in presence of 0.1 mM inhibitor
3-(3-(2-(9H-pyrido[3,4-b]indol-9-yl)ethyl)ureido)benzoic acid
36% inhibition at 0.1 mM
3-chloro-5-(3,4-dimethoxyphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-2-carboxylic acid
30.85% inhibition at 0.1 mM
3-hydroxy-5-(morpholine-4-sulfonyl)naphthalene-2-carboxylic acid
9.2% inhibition at 0.1 mM
3-hydroxy-5-[(prop-2-en-1-yl)sulfamoyl]naphthalene-2-carboxylic acid
17.43% inhibition at 0.1 mM
3-[5-[2-cyano-3-(3,4-dimethylanilino)-3-oxopropyl]furan-2-yl]benzoic acid
-
4-(((2-(9H-pyrido[3,4-b]indol-9-yl)ethyl)amino)methyl)benzoic acid
22% inhibition at 0.1 mM
4-((2-(9H-pyrido[3,4-b]indol-9-yl)acetamido)methyl)benzoic acid
25% inhibition at 0.1 mM
4-((2-(9H-pyrido[3,4-b]indol-9-yl)ethyl)carbamoyl)benzoic acid
25% inhibition at 0.1 mM
4-(3,4-dimethyl-6-oxopyrano[2,3-c]pyrazol-1(6H)-yl)benzoic acid
18.70% inhibition at 0.1 mM
4-(3-(2-(9H-pyrido[3,4-b]indol-9-yl)ethyl)ureido)benzoic acid
52% inhibition at 0.1 mM
4-(5-[(1E)-2-cyano-3-[3-(methylcarbamoyl)anilino]-3-oxoprop-1-en-1-yl]furan-2-yl)benzoic acid
4-(5-[(1E)-2-cyano-3-[4-cyano-3-(trifluoromethyl)anilino]-3-oxoprop-1-en-1-yl]furan-2-yl)benzoic acid
4-(5-[(1E)-3-[4-chloro-3-(trifluoromethyl)anilino]-2-cyano-3-oxoprop-1-en-1-yl]furan-2-yl)benzoic acid
4-(5-[(Z)-[1-(3-chloro-4-methylphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)benzoic acid
4-(5-[2-cyano-3-[(2,3-dihydro-1,4-benzodioxin-6-yl)amino]-3-oxopropyl]furan-2-yl)benzoic acid
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4-(5-[2-cyano-3-[3-(methylcarbamoyl)anilino]-3-oxopropyl]furan-2-yl)benzoic acid
-
4-(5-[2-cyano-3-[4-cyano-3-(trifluoromethyl)anilino]-3-oxopropyl]furan-2-yl)benzoic acid
-
4-(5-[3-[(2H-1,3-benzodioxol-5-yl)amino]-2-cyano-3-oxopropyl]furan-2-yl)benzoic acid
-
4-(5-[3-[4-chloro-3-(trifluoromethyl)anilino]-2-cyano-3-oxopropyl]furan-2-yl)benzoic acid
-
4-(6-tert-butyl-2H-1,3-benzoxazin-3(4H)-yl)benzoic acid
24.54% inhibition at 0.1 mM
4-([(Z)-[2-(2-bromophenyl)-5-oxo-1,3-oxazol-4(5H)-ylidene]methyl]amino)benzoic acid
34.24% inhibition at 0.1 mM
4-[(3-[[(2-carboxyethyl)carbamothioyl]amino]propyl)amino]-2-[[2-(1H-indol-3-yl)ethyl]amino]pyrimidine-5-carboxylic acid
4-[(4Z)-3-methyl-5-oxo-4-[(2E)-3-phenylprop-2-en-1-ylidene]-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid
77.26% inhibition at 0.1 mM
4-[(E)-(6-hydroxyquinolin-5-yl)diazenyl]benzoic acid
61.3% inhibition at 0.1 mM
4-[(E)-[(4-bromo-3-chloro-2-hydroxyphenyl)methylidene]amino]benzoic acid
33.66% inhibition at 0.1 mM
4-[5-[(1E)-2-cyano-3-(3,4-dimethylanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]-3-methylbenzoic acid
4-[5-[(1E)-2-cyano-3-(4-cyano-3-fluoroanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid
4-[5-[(1E)-3-(4-chloro-3-nitroanilino)-2-cyano-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid
4-[5-[2-cyano-3-(3,4-dimethoxyanilino)-3-oxopropyl]furan-2-yl]benzoic acid
-
4-[5-[2-cyano-3-(3,4-dimethylanilino)-3-oxopropyl]furan-2-yl]-3-fluorobenzoic acid
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4-[5-[2-cyano-3-(3,4-dimethylanilino)-3-oxopropyl]furan-2-yl]-3-methylbenzoic acid
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4-[5-[2-cyano-3-(3,4-dimethylanilino)-3-oxopropyl]furan-2-yl]benzoic acid
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4-[5-[2-cyano-3-(3,5-dichloroanilino)-3-oxopropyl]furan-2-yl]benzoic acid
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4-[5-[2-cyano-3-(3,5-dimethylanilino)-3-oxopropyl]furan-2-yl]benzoic acid
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4-[5-[3-(3-acetamidoanilino)-2-cyano-3-oxopropyl]furan-2-yl]benzoic acid
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5-(1H-indol-3-ylmethylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
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5-(4-hydroxy-2,2-dimethyloxan-4-yl)-1,2-oxazole-3-carboxylic acid
17.41% inhibition at 0.1 mM
5-(4-methylphenyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine-2-carboxylic acid
11.08% inhibition at 0.1 mM
5-(biphenyl-4-ylmethylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
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5-([4-[(2-chlorophenyl)methoxy]-3-methoxyphenyl]methylidene)-2-sulfanylidene-1,3-diazinane-4,6-dione
5-[(1-benzyl-1H-indol-3-yl)methylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
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5-[(5-[[(benzyloxy)carbonyl]amino]-6-[(diphenylmethyl)amino]-6-oxohexyl)amino]-5-sulfanylidenepentanoic acid
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5-[(5-[[(benzyloxy)carbonyl]amino]-6-[[(naphthalen-1-yl)methyl]amino]-6-oxohexyl)amino]-5-sulfanylidenepentanoic acid
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5-[(5-[[(benzyloxy)carbonyl]amino]-6-[[2-(1H-indol-3-yl)ethyl]amino]-6-oxohexyl)amino]-5-sulfanylidenepentanoic acid
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5-[(6-amino-5-[[(benzyloxy)carbonyl]amino]-6-oxohexyl)amino]-5-sulfanylidenepentanoic acid
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5-[(6-methoxynaphthalen-1-yl)methylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
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5-[(6-[(1,3-benzothiazol-5-yl)amino]-5-[[(benzyloxy)carbonyl]amino]-6-oxohexyl)amino]-5-sulfanylidenepentanoic acid
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5-[(6-[(adamantan-1-yl)amino]-5-[[(benzyloxy)carbonyl]amino]-6-oxohexyl)amino]-5-sulfanylidenepentanoic acid
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5-[(E)-(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)diazenyl]-4H-pyrazole-3-carboxylic acid
70.03% inhibition at 0.1 mM
5-[4-(benzyloxy)benzylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
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5-[4-(propan-2-yl)benzylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
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5-[4-[(2-chlorobenzyl)oxy]-3-methoxybenzylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
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5-[4-[(4-bromobenzyl)oxy]benzylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
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5-[[5-(2,3-dichlorophenyl)furan-2-yl]methylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
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5-[[5-[[(benzyloxy)carbonyl]amino]-6-oxo-6-([(1S)-2-oxo-1-phenyl-2-[(propan-2-yl)amino]ethyl]amino)hexyl]amino]-5-sulfanylidenepentanoic acid
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6-carboxy-5-methyl-3-[2-(3-methylpiperidin-1-yl)-2-oxoethyl]-4-oxo-4,4a-dihydrothieno[2,3-d]pyrimidin-3-ium
15.43% inhibition at 0.1 mM
6-[(3-[[(2-carboxyethyl)carbamothioyl]amino]propyl)amino]-2-[[2-(1H-indol-3-yl)ethyl]amino]pyrimidine-4-carboxylic acid
7-(diethylamino)-2-oxo-2H-1-benzopyran-3-carboxylic acid
28.91% inhibition at 0.1 mM
ethyl 4-[[2-(9H-pyrido[3,4-b]indol-9-yl)acetamido]methyl]benzoate
12% inhibition at 0.1 mM
L-lysyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-N6-(3-carboxypropanethioyl)-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanine
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methyl 4-[5-[2-cyano-3-(3,4-dimethylanilino)-3-oxopropyl]furan-2-yl]benzoate
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N-(4-chlorobenzyl)-2-(9H-pyrido[3,4-b]indol-9-yl)acetamide
18% inhibition at 0.1 mM
N-(pyridin-3-ylmethyl)-2-(9H-pyrido[3,4-b]indol-9-yl)acetamide
24% inhibition at 0.1 mM
N-([3-[(2-[[2-(1H-indol-3-yl)ethyl]amino]-5-nitropyrimidin-4-yl)amino]propyl]carbamothioyl)-beta-alanine
N-([4-[(2S,5R,27S)-27-acetamido-8-[[(2R,3S)-1-amino-3-hydroxy-1-oxobutan-2-yl]carbamoyl]-2-(3-carbamimidamidopropyl)-3,6,14,21,28-pentaoxo-1,4,7,13,22-pentaazacyclooctacosan-5-yl]butyl]carbamothioyl)-beta-alanine
-
N-([4-[(3S,6S,16S)-6-(3-carbamimidamidopropyl)-16-carbamoyl-2,5,8,11-tetraoxo-1,4,7,12-tetraazacyclohexadecan-3-yl]butyl]carbamothioyl)-beta-alanine
-
N-([4-[(3S,6S,17S)-17-carbamoyl-2,5,8,11-tetraoxo-6-propyl-1,4,7,12-tetraazacycloheptadecan-3-yl]butyl]carbamothioyl)-beta-alanine
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N-([4-[(3S,6S,17S)-6-(3-carbamimidamidopropyl)-17-carbamoyl-2,5,8,11-tetraoxo-1,4,7,12-tetraazacycloheptadecan-3-yl]butyl]carbamothioyl)-beta-alanine
-
N-([4-[(3S,6S,18S)-6-(3-carbamimidamidopropyl)-18-carbamoyl-2,5,8,12-tetraoxo-1,4,7,13-tetraazacyclooctadecan-3-yl]butyl]carbamothioyl)-beta-alanine
-
N-([4-[(3S,6S,9S)-9-acetamido-27-[[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]carbamoyl]-6-(3-carbamimidamidopropyl)-2,5,8,14,21-pentaoxo-1,4,7,13,22-pentaazacycloheptacosan-3-yl]butyl]carbamothioyl)-beta-alanine
-
N-([4-[(5S,8S,11S)-5-(3-carbamimidamidopropyl)-11-carbamoyl-3,6,9,17-tetraoxo-4,7,10,16-tetraazabicyclo[17.2.2]tricosa-1(21),19,22-trien-8-yl]butyl]carbamothioyl)-beta-alanine
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N-acetyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(naphthalen-2-yl)sulfanyl]propanoyl]-L-lysyl-L-alaninamide
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N-acetyl-L-leucyl-N6-[3-carboxy-3-[(naphthalen-2-yl)sulfanyl]propanoyl]-L-lysyl-L-alaninamide
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N-benzyl-2-(9H-pyrido[3,4-b]indol-9-yl)ethan-1-amine
10% inhibition at 0.1 mM
N-benzylglycyl-L-valyl-L-leucyl-N6-(3-carboxy-3-phenylbutanoyl)-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
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N-benzylglycylglycyl-L-valyl-L-leucyl-N6-(3-carboxy-3-[[2-(pyrazin-2-yl)ethyl]sulfanyl]propanoyl)-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
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N-benzylglycylglycyl-L-valyl-L-leucyl-N6-(3-carboxy-3-[[2-(pyridin-2-yl)ethyl]sulfanyl]propanoyl)-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
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N-benzylglycylglycyl-L-valyl-L-leucyl-N6-(3-carboxy-3-[[2-(pyridin-4-yl)ethyl]sulfanyl]propanoyl)-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
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N-benzylglycylglycyl-L-valyl-L-leucyl-N6-(3-carboxy-4-phenylbutanoyl)-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-(benzylsulfanyl)-3-carboxypropanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-(cyclohexylsulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-(phenylsulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-([[3-(trifluoromethyl)phenyl]methyl]sulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-([[4-(trifluoromethyl)phenyl]methyl]sulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(2,3-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(2,4-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(2,6-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(2-chlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(2-phenylethyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
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N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(3,4-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(3,4-dimethylphenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(3,5-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(3-chlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(3-phenylpropyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(4-chlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(naphthalen-1-yl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(naphthalen-2-yl)sulfanyl]butanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(naphthalen-2-yl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[(2,4,6-trimethylphenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[(2,4-dichlorophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[(2-chlorophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[(3,4-dichlorophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[(3-nitrophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[(4-chlorophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[(4-methoxyphenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[(4-nitrophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[(naphthalen-1-yl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-[[(4-tert-butylphenyl)methyl]sulfanyl]-3-carboxypropanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R-3-carboxy-3-[(3,4-dimethoxyphenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-(benzylsulfanyl)-3-carboxypropanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-(cyclohexylsulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-(phenylsulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-([[3-(trifluoromethyl)phenyl]methyl]sulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-([[4-(trifluoromethyl)phenyl]methyl]sulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(2,3-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(2,4-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(2,5-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(2,6-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(2-chlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(2-phenylethyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(3,4-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(3,4-dimethoxyphenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(3,4-dimethylphenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(3,5-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(3-chlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(3-phenylpropyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(4-chlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(naphthalen-1-yl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(naphthalen-2-yl)sulfanyl]butanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(naphthalen-2-yl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[(2,4,6-trimethylphenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[(2,4-dichlorophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[(2-chlorophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[(3,4-dichlorophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[(3-nitrophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[(4-chlorophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[(4-methoxyphenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[(4-nitrophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[(naphthalen-1-yl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-[[(4-tert-butylphenyl)methyl]sulfanyl]-3-carboxypropanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[3-[(naphthalen-2-yl)sulfanyl]butanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[3-[(naphthalen-2-yl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-[(3-[[2-(benzylamino)-5-(ethoxycarbonyl)pyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine
N-[(3-[[5-(ethoxycarbonyl)-2-[[2-(1H-indol-3-yl)ethyl]amino]pyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine
N-[(7S)-7-[[(benzyloxy)carbonyl]amino]-8-([(2S)-3-(1H-indol-3-yl)-1-oxo-1-[(propan-2-yl)amino]propan-2-yl]amino)-8-oxooctanoyl]-beta-alanine
-
N-[(benzyloxy)carbonyl]-5-[2-(4-carboxybutanoyl)hydrazinyl]-L-norvalyl-N-propan-2-yl-L-tryptophanamide
-
N-[5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoyl]-L-threonyl-L-threonyl-L-alpha-aspartyl-L-serylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(naphthalen-2-yl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-[5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoyl]-L-threonyl-L-threonyl-L-alpha-aspartyl-L-serylglycyl-L-valyl-L-leucyl-N6-[3-carboxy-3-[(naphthalen-2-yl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-[[3-([5-nitro-2-[(2-phenylethyl)amino]pyrimidin-4-yl]amino)propyl]carbamothioyl]-beta-alanine
N2-(benzenesulfonyl)-N6-[(2-carboxyethyl)carbamothioyl]-L-lysyl-L-tryptophanamide
-
N2-(benzylcarbamoyl)-N6-[(2-carboxyethyl)carbamothioyl]-L-lysyl-L-tryptophanamide
-
N2-acetyl-L-arginyl-N6-[(2-carboxyethyl)carbamothioyl]-L-lysyl-N6-acetyl-L-lysinamide
-
N2-benzoyl-N6-[(2-carboxyethyl)carbamothioyl]-L-lysyl-L-tryptophanamide
-
N2-[(benzyloxy)carbonyl]-N6-(4-carboxy-2,2-difluorobutanoyl)-L-lysyl-N-propan-2-yl-L-tryptophanamide
-
N2-[(benzyloxy)carbonyl]-N6-(4-carboxybutanethioyl)lysyl-L-tryptophanamide
-
N2-[(benzyloxy)carbonyl]-N6-(4-carboxybutanethioyl)lysyl-L-tryptophyl-L-aspartamide
-
N2-[(benzyloxy)carbonyl]-N6-(4-carboxybutanethioyl)lysyl-L-tryptophyl-L-phenylalaninamide
-
N2-[(benzyloxy)carbonyl]-N6-(4-carboxybutanethioyl)lysyl-L-tyrosinamide
-
N2-[(benzyloxy)carbonyl]-N6-(4-carboxybutanethioyl)lysyl-N-propan-2-yl-D-tryptophanamide
-
N2-[(benzyloxy)carbonyl]-N6-(4-carboxybutanethioyl)lysyl-N-propan-2-yl-L-alaninamide
-
N2-[(benzyloxy)carbonyl]-N6-(4-carboxybutanethioyl)lysyl-N-propan-2-yl-L-prolinamide
-
N2-[(benzyloxy)carbonyl]-N6-(4-carboxybutanethioyl)lysyl-N-propan-2-yl-L-tryptophanamide
enzyme binding structure, crystal structure analysis
N2-[(benzyloxy)carbonyl]-N6-(4-carboxybutanethioyl)lysyl-N-[(2S)-1,4-diamino-1-oxobutan-2-yl]-L-tryptophanamide
-
N2-[(benzyloxy)carbonyl]-N6-ethanethioyl-L-lysyl-N-propan-2-yl-L-tryptophanamide
-
N2-[(benzyloxy)carbonyl]-N6-[(2-carboxyethoxy)carbonyl]-L-lysyl-N-propan-2-yl-L-tryptophanamide
-
N2-[(benzyloxy)carbonyl]-N6-[(2-carboxyethyl)carbamothioyl]-L-lysyl-L-tryptophanamide
-
N2-[(benzyloxy)carbonyl]-N6-[(2-carboxyethyl)carbamothioyl]-L-lysyl-N-adamantan-1-yl-L-tryptophanamide
-
N2-[(benzyloxy)carbonyl]-N6-[(2-carboxyethyl)carbamothioyl]-L-lysyl-N-cyclopropyl-L-tryptophanamide
-
N2-[(benzyloxy)carbonyl]-N6-[(2-carboxyethyl)carbamothioyl]-L-lysyl-N-propan-2-yl-L-tryptophanamide
enzyme binding structure, crystal structure analysis
N2-[(benzyloxy)carbonyl]-N6-[(2-carboxyethyl)carbamothioyl]-L-lysyl-N-[(2S)-1-methoxy-3-phenylpropan-2-yl]-L-tryptophanamide
-
N2-[(benzyloxy)carbonyl]-N6-[(2-carboxyethyl)carbamoyl]-L-lysyl-N-propan-2-yl-L-tryptophanamide
-
N2-[(benzyloxy)carbonyl]-N6-[(3R)-4-carboxy-3-methylbutanoyl]-L-lysyl-N-propan-2-yl-L-tryptophanamide
-
N2-[(benzyloxy)carbonyl]-N6-[(3S)-4-carboxy-3-methylbutanoyl]-L-lysyl-N-propan-2-yl-L-tryptophanamide
-
N2-[(benzyloxy)carbonyl]-N6-[(carboxymethyl)carbamothioyl]-L-lysyl-N-propan-2-yl-L-tryptophanamide
-
N6-[(2-carboxyethyl)carbamothioyl]-N2-(3-fluorobenzene-1-sulfonyl)-L-lysyl-L-tryptophanamide
-
N6-[(2-carboxyethyl)carbamothioyl]-N2-(3-fluorobenzene-1-sulfonyl)-L-lysyl-N-cyclobutyl-L-tryptophanamide
-
N6-[(2-carboxyethyl)carbamothioyl]-N2-(3-fluorobenzene-1-sulfonyl)-L-lysyl-N-cyclopentyl-L-tryptophanamide
-
N6-[(2-carboxyethyl)carbamothioyl]-N2-(3-fluorobenzene-1-sulfonyl)-L-lysyl-N-cyclopropyl-L-tryptophanamide
-
N6-[(2-carboxyethyl)carbamothioyl]-N2-(3-phenylpropanoyl)-L-lysyl-L-tryptophanamide
-
N6-[(2-carboxyethyl)carbamothioyl]-N2-(4-methoxybenzene-1-sulfonyl)-L-lysyl-L-tryptophanamide
-
N6-[(2-carboxyethyl)carbamothioyl]-N2-(4-nitrobenzene-1-sulfonyl)-L-lysyl-L-tryptophanamide
-
N6-[(2-carboxyethyl)carbamothioyl]-N2-(naphthalene-2-sulfonyl)-L-lysyl-L-tryptophanamide
-
N6-[(2-carboxyethyl)carbamothioyl]-N2-(phenylacetyl)-L-lysyl-L-tryptophanamide
-
N6-[(2-carboxyethyl)carbamothioyl]-N2-(phenylcarbamoyl)-L-lysyl-L-tryptophanamide
-
N6-[(2-carboxyethyl)carbamothioyl]-N2-(quinoline-8-sulfonyl)-L-lysyl-L-tryptophanamide
-
N6-[(2-carboxyethyl)carbamothioyl]-N2-[4-(trifluoromethyl)benzene-1-sulfonyl]-L-lysyl-L-tryptophanamide
-
N6-[N-[(benzyloxy)carbonyl]-L-gamma-glutamyl]-N2-[(benzyloxy)carbonyl]-L-lysyl-N-propan-2-yl-L-tryptophanamide
-
(5E)-5-[[4-(benzyloxy)phenyl]methylidene]-1-(prop-2-en-1-yl)-2-sulfanylidene-1,3-diazinane-4,6-dione
-
(5E)-5-[[4-(benzyloxy)phenyl]methylidene]-1-(prop-2-en-1-yl)-2-sulfanylidene-1,3-diazinane-4,6-dione
-
(5E)-5-[[4-(benzyloxy)phenyl]methylidene]-1-ethyl-2-sulfanylidene-1,3-diazinane-4,6-dione
-
(5E)-5-[[4-(benzyloxy)phenyl]methylidene]-1-ethyl-2-sulfanylidene-1,3-diazinane-4,6-dione
-
(5E)-5-[[4-(benzyloxy)phenyl]methylidene]-1-methyl-2-sulfanylidene-1,3-diazinane-4,6-dione
-
(5E)-5-[[4-(benzyloxy)phenyl]methylidene]-1-methyl-2-sulfanylidene-1,3-diazinane-4,6-dione
-
(5E)-5-[[5-(2,3-dichlorophenyl)furan-2-yl]methylidene]-1-(prop-2-en-1-yl)-2-sulfanylidene-1,3-diazinane-4,6-dione
-
(5E)-5-[[5-(2,3-dichlorophenyl)furan-2-yl]methylidene]-1-(prop-2-en-1-yl)-2-sulfanylidene-1,3-diazinane-4,6-dione
-
3-[5-[(1E)-2-cyano-3-(3,4-dimethylanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid
-
3-[5-[(1E)-2-cyano-3-(3,4-dimethylanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid
-
4-(5-[(1E)-2-cyano-3-[3-(methylcarbamoyl)anilino]-3-oxoprop-1-en-1-yl]furan-2-yl)benzoic acid
-
4-(5-[(1E)-2-cyano-3-[3-(methylcarbamoyl)anilino]-3-oxoprop-1-en-1-yl]furan-2-yl)benzoic acid
-
4-(5-[(1E)-2-cyano-3-[4-cyano-3-(trifluoromethyl)anilino]-3-oxoprop-1-en-1-yl]furan-2-yl)benzoic acid
-
4-(5-[(1E)-2-cyano-3-[4-cyano-3-(trifluoromethyl)anilino]-3-oxoprop-1-en-1-yl]furan-2-yl)benzoic acid
-
4-(5-[(1E)-3-[4-chloro-3-(trifluoromethyl)anilino]-2-cyano-3-oxoprop-1-en-1-yl]furan-2-yl)benzoic acid
-
4-(5-[(1E)-3-[4-chloro-3-(trifluoromethyl)anilino]-2-cyano-3-oxoprop-1-en-1-yl]furan-2-yl)benzoic acid
-
4-(5-[(Z)-[1-(3-chloro-4-methylphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)benzoic acid
94.3% inhibition at 0.1 mM
4-(5-[(Z)-[1-(3-chloro-4-methylphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)benzoic acid
-
4-(5-[(Z)-[1-(3-chloro-4-methylphenyl)-3-methyl-5-oxo-1,5-dihydro-4H-pyrazol-4-ylidene]methyl]furan-2-yl)benzoic acid
-
4-[(3-[[(2-carboxyethyl)carbamothioyl]amino]propyl)amino]-2-[[2-(1H-indol-3-yl)ethyl]amino]pyrimidine-5-carboxylic acid
-
4-[(3-[[(2-carboxyethyl)carbamothioyl]amino]propyl)amino]-2-[[2-(1H-indol-3-yl)ethyl]amino]pyrimidine-5-carboxylic acid
-
4-[5-[(1E)-2-cyano-3-(3,4-dimethylanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]-3-methylbenzoic acid
-
4-[5-[(1E)-2-cyano-3-(3,4-dimethylanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]-3-methylbenzoic acid
-
4-[5-[(1E)-2-cyano-3-(3,4-dimethylanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid
-
4-[5-[(1E)-2-cyano-3-(3,4-dimethylanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid
-
4-[5-[(1E)-2-cyano-3-(3,5-dimethylanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid
-
4-[5-[(1E)-2-cyano-3-(3,5-dimethylanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid
-
4-[5-[(1E)-2-cyano-3-(4-cyano-3-fluoroanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid
-
4-[5-[(1E)-2-cyano-3-(4-cyano-3-fluoroanilino)-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid
-
4-[5-[(1E)-3-(4-chloro-3-nitroanilino)-2-cyano-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid
97.14% inhibition at 0.1 mM
4-[5-[(1E)-3-(4-chloro-3-nitroanilino)-2-cyano-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid
-
4-[5-[(1E)-3-(4-chloro-3-nitroanilino)-2-cyano-3-oxoprop-1-en-1-yl]furan-2-yl]benzoic acid
-
4-[5-[2-cyano-3-(4-cyano-3-fluoroanilino)-3-oxopropyl]furan-2-yl]benzoic acid
competitive inhibitor
4-[5-[2-cyano-3-(4-cyano-3-fluoroanilino)-3-oxopropyl]furan-2-yl]benzoic acid
-
5-([4-[(2-chlorophenyl)methoxy]-3-methoxyphenyl]methylidene)-2-sulfanylidene-1,3-diazinane-4,6-dione
-
5-([4-[(2-chlorophenyl)methoxy]-3-methoxyphenyl]methylidene)-2-sulfanylidene-1,3-diazinane-4,6-dione
-
5-([4-[(4-bromophenyl)methoxy]phenyl]methylidene)-2-sulfanylidene-1,3-diazinane-4,6-dione
-
5-([4-[(4-bromophenyl)methoxy]phenyl]methylidene)-2-sulfanylidene-1,3-diazinane-4,6-dione
-
5-[[4-(benzyloxy)phenyl]methylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione
-
5-[[4-(benzyloxy)phenyl]methylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione
-
5-[[5-(2,3-dichlorophenyl)furan-2-yl]methylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione
-
5-[[5-(2,3-dichlorophenyl)furan-2-yl]methylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione
-
6-[(3-[[(2-carboxyethyl)carbamothioyl]amino]propyl)amino]-2-[[2-(1H-indol-3-yl)ethyl]amino]pyrimidine-4-carboxylic acid
-
6-[(3-[[(2-carboxyethyl)carbamothioyl]amino]propyl)amino]-2-[[2-(1H-indol-3-yl)ethyl]amino]pyrimidine-4-carboxylic acid
-
N-([3-[(2-[[2-(1H-indol-3-yl)ethyl]amino]-5-nitropyrimidin-4-yl)amino]propyl]carbamothioyl)-beta-alanine
-
N-([3-[(2-[[2-(1H-indol-3-yl)ethyl]amino]-5-nitropyrimidin-4-yl)amino]propyl]carbamothioyl)-beta-alanine
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-(benzylsulfanyl)-3-carboxypropanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-(benzylsulfanyl)-3-carboxypropanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-(phenylsulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-(phenylsulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-(benzylsulfanyl)-3-carboxypropanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-(benzylsulfanyl)-3-carboxypropanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-(phenylsulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-(phenylsulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
-
N-[(3-[[2-(benzylamino)-5-(ethoxycarbonyl)pyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine
-
N-[(3-[[2-(benzylamino)-5-(ethoxycarbonyl)pyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine
-
N-[(3-[[2-(benzylamino)-5-fluoropyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine
-
N-[(3-[[2-(benzylamino)-5-fluoropyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine
-
N-[(3-[[2-(benzylamino)-5-nitropyridin-4-yl]amino]propyl)carbamothioyl]-beta-alanine
-
N-[(3-[[2-(benzylamino)-5-nitropyridin-4-yl]amino]propyl)carbamothioyl]-beta-alanine
-
N-[(3-[[2-(benzylamino)-5-nitropyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine
-
N-[(3-[[2-(benzylamino)-5-nitropyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine
-
N-[(3-[[2-(benzylamino)pyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine
-
N-[(3-[[2-(benzylamino)pyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine
-
N-[(3-[[5-(ethoxycarbonyl)-2-[[2-(1H-indol-3-yl)ethyl]amino]pyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine
-
N-[(3-[[5-(ethoxycarbonyl)-2-[[2-(1H-indol-3-yl)ethyl]amino]pyrimidin-4-yl]amino]propyl)carbamothioyl]-beta-alanine
-
N-[(3-[[6-(benzylamino)-3-nitropyridin-2-yl]amino]propyl)carbamothioyl]-beta-alanine
-
N-[(3-[[6-(benzylamino)-3-nitropyridin-2-yl]amino]propyl)carbamothioyl]-beta-alanine
-
N-[[3-([5-nitro-2-[(2-phenylethyl)amino]pyrimidin-4-yl]amino)propyl]carbamothioyl]-beta-alanine
-
N-[[3-([5-nitro-2-[(2-phenylethyl)amino]pyrimidin-4-yl]amino)propyl]carbamothioyl]-beta-alanine
-
nicotinamide
nicotinamide inhibition of Sirt5-dependent deacetylation features weak substrate-dependence but requires high, nonphysiological nicotinamide concentrations. The insensitivity of Sirt5 to physiological nicotinamide concentrations is due to a lack of non-competitive inhibition via base exchange, and the inhibition observed at very high nicotinamide concentrations is likely caused by competition with NAD+
suramin
suramin binds into the NAD+-, the product-, and the substrate-binding site
additional information
the acyl-substrate specificity of SIRT5 is adapted to selectively inhibit this isozyme. Synthesis and evaluation of mechanism-based inhibitors of SIRT5, structure-activity relationship, overview
-
additional information
-
the acyl-substrate specificity of SIRT5 is adapted to selectively inhibit this isozyme. Synthesis and evaluation of mechanism-based inhibitors of SIRT5, structure-activity relationship, overview
-
additional information
H3K9TAc and sirtinol show no inhibnition at 0.1 mM
-
additional information
not inhibited by EX527 (i.e. 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide)
-
additional information
-
not inhibited by EX527 (i.e. 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide)
-
additional information
the acyl-substrate specificity of SIRT5 is adapted to selectively inhibit this isozyme. Synthesis and evaluation of mechanism-based inhibitors of SIRT5, structure-activity relationship, overview
-
additional information
-
the acyl-substrate specificity of SIRT5 is adapted to selectively inhibit this isozyme. Synthesis and evaluation of mechanism-based inhibitors of SIRT5, structure-activity relationship, overview
-
additional information
no inhibition by (2E)-4,4-dihydroxy-N-[4-[(5-methyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]but-2-enamide; structure-based discovery of selective small-molecul sirtuin 5 inhibitors. Synthesis of (E)-2-cyano-N-phenyl-3-(5-phenylfuran-2-yl)acrylamide derivatives/analogues, docking study, structure-activity relationship analyses, overview. No inhibition by 14 at 0.1 mM
-
additional information
-
no inhibition by (2E)-4,4-dihydroxy-N-[4-[(5-methyl-1,2-oxazol-3-yl)sulfamoyl]phenyl]but-2-enamide; structure-based discovery of selective small-molecul sirtuin 5 inhibitors. Synthesis of (E)-2-cyano-N-phenyl-3-(5-phenylfuran-2-yl)acrylamide derivatives/analogues, docking study, structure-activity relationship analyses, overview. No inhibition by 14 at 0.1 mM
-
additional information
SIRT can be targeted by small molecules, structure-activity relationship study leading to identification of SIRT5 selective inhibitors that exhibit sub-micromolar potency via a slow, tight-binding mechanism
-
additional information
design and synthesis of 9-substituted norharmane derivatives as potential Sirt5 inhibitors, molceular docking, overview
-
additional information
analysis of potent and selective inhibitors of human sirtuin 5, screening and synthesis of 3-arylthiosuccinylated and 3-benzylthiosuccinylated peptide derivatives yielding Sirt5 inhibitors with low-nanomolar Ki values, overview. Crystal structures of Sirt5/ inhibitor complexes reveal that the compounds bind in to the active site of Sirt5. Molecular docking study, computational analysis
-
additional information
-
analysis of potent and selective inhibitors of human sirtuin 5, screening and synthesis of 3-arylthiosuccinylated and 3-benzylthiosuccinylated peptide derivatives yielding Sirt5 inhibitors with low-nanomolar Ki values, overview. Crystal structures of Sirt5/ inhibitor complexes reveal that the compounds bind in to the active site of Sirt5. Molecular docking study, computational analysis
-
additional information
SIRT can be targeted by small molecules, structure-activity relationship study leading to identification of SIRT5 selective inhibitors that exhibited sub-micromolar potency via a slow, tight-binding mechanism
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
resveratrol
0.2 mM resveratrol can stimulate the Sirt5 deacetylase activity against the fluorophore-modified peptide substrate Fluor-de-Lys
cardiolipin
SIRT5 electrostatically binds to cardiolipin, an N-terminal amphipathic helix mediates SIRT5 binding to cardiolipin, cardiolipin activates desuccinylation of membrane proteins
cardiolipin
SIRT5 electrostatically binds to cardiolipin, an N-terminal amphipathic helix mediates SIRT5 binding to cardiolipin, cardiolipin activates desuccinylation of membrane proteins
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.08018
[histone H2A]-N6-succinyl-L-lysine95
pH 7.5, 37°C, recombinant enzyme
-
0.10228
[histone H2A]-N6-succinyl-L-lysine9_(4-15)-A10G peptide
pH 7.5, 37°C, recombinant enzyme
-
0.06173
[histone H2B]-N6-succinyl-L-lysine116
pH 7.5, 37°C, recombinant enzyme
-
0.08777
[histone H2B]-N6-succinyl-L-lysine120
pH 7.5, 37°C, recombinant enzyme
-
0.09973
[histone H2B]-N6-succinyl-L-lysine34
pH 7.5, 37°C, recombinant enzyme
-
0.086
[histone H3 K9 peptide]-N6-succinyl-L-lysine
-
pH 8.0, 37°C, wild-type enzyme
-
0.06051
[histone H3]-N6-succinyl-L-lysine122
pH 7.5, 37°C, recombinant enzyme
-
0.09551
[histone H3]-N6-succinyl-L-lysine14
pH 7.5, 37°C, recombinant enzyme
-
0.10442
[histone H3]-N6-succinyl-L-lysine14_(9-20)-A15G peptide
pH 7.5, 37°C, recombinant enzyme
-
0.17932
[histone H3]-N6-succinyl-L-lysine56
pH 7.5, 37°C, recombinant enzyme
-
0.08489
[histone H3]-N6-succinyl-L-lysine79
pH 7.5, 37°C, recombinant enzyme
-
0.07717
[histone H3]-N6-succinyl-L-lysine9
pH 7.5, 37°C, recombinant enzyme
-
0.10072
[histone H4]-N6-succinyl-L-lysine12
pH 7.5, 37°C, recombinant enzyme
-
0.13153
[histone H4]-N6-succinyl-L-lysine31
pH 7.5, 37°C, recombinant enzyme
-
0.06583
[histone H4]-N6-succinyl-L-lysine31_(26-37)-P32A peptide
pH 7.5, 37°C, recombinant enzyme
-
0.08268
[histone H4]-N6-succinyl-L-lysine77
pH 7.5, 37°C, recombinant enzyme
-
0.10178
[histone H4]-N6-succinyl-L-lysine91
pH 7.5, 37°C, recombinant enzyme
-
0.72
[protein]-N6-acetyl-L-lysine
mutant enzyme Y102A, at 8.0 pH and 25°C
0.069
NAD+
wild type enzyme, with [protein]-N6-succinyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
0.15
NAD+
cosubstrate: Ac-(N6-succinyl)Lys-7-amido-4-methylcoumarin, pH 8.0, 37°C
0.321
NAD+
mutant enzyme Y102A, with [protein]-N6-succinyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
0.609
NAD+
mutant enzyme R105I, with [protein]-N6-acetyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
1.194
NAD+
mutant enzyme Y102A/R105I, with [protein]-N6-acetyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
1.605
NAD+
mutant enzyme Y102A, with [protein]-N6-acetyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
0.0147
[histone H3 K9 peptide]-N6-acetyl-L-lysine
-
pH 8.0, 37°C, mutant enzyme Y92F
-
0.0151
[histone H3 K9 peptide]-N6-acetyl-L-lysine
-
pH 8.0, 37°C, wild-type enzyme
-
0.02
[histone H3 K9 peptide]-N6-acetyl-L-lysine
-
pH 8.0, 37°C, mutant enzyme R95M
-
0.388
[protein]-N6-succinyl-L-lysine
mutant enzyme Y102A/R105I, at 8.0 pH and 25°C
1.658
[protein]-N6-succinyl-L-lysine
mutant enzyme R105I, at 8.0 pH and 25°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.219
[histone H2A]-N6-succinyl-L-lysine95
pH 7.5, 37°C, recombinant enzyme
-
0.199
[histone H2A]-N6-succinyl-L-lysine9_(4-15)-A10G peptide
pH 7.5, 37°C, recombinant enzyme
-
0.297
[histone H2B]-N6-succinyl-L-lysine116
pH 7.5, 37°C, recombinant enzyme
-
0.279
[histone H2B]-N6-succinyl-L-lysine120
pH 7.5, 37°C, recombinant enzyme
-
0.314
[histone H2B]-N6-succinyl-L-lysine34
pH 7.5, 37°C, recombinant enzyme
-
0.242
[histone H3 K9 peptide]-N6-succinyl-L-lysine
-
pH 8.0, 37°C, wild-type enzyme
-
0.178
[histone H3]-N6-succinyl-L-lysine122
pH 7.5, 37°C, recombinant enzyme
-
0.2
[histone H3]-N6-succinyl-L-lysine14
pH 7.5, 37°C, recombinant enzyme
-
0.186
[histone H3]-N6-succinyl-L-lysine14_(9-20)-A15G peptide
pH 7.5, 37°C, recombinant enzyme
-
0.512
[histone H3]-N6-succinyl-L-lysine56
pH 7.5, 37°C, recombinant enzyme
-
0.213
[histone H3]-N6-succinyl-L-lysine79
pH 7.5, 37°C, recombinant enzyme
-
0.336
[histone H3]-N6-succinyl-L-lysine9
pH 7.5, 37°C, recombinant enzyme
-
0.202
[histone H4]-N6-succinyl-L-lysine12
pH 7.5, 37°C, recombinant enzyme
-
0.224
[histone H4]-N6-succinyl-L-lysine31
pH 7.5, 37°C, recombinant enzyme
-
0.189
[histone H4]-N6-succinyl-L-lysine31_(26-37)-P32A peptide
pH 7.5, 37°C, recombinant enzyme
-
0.208
[histone H4]-N6-succinyl-L-lysine77
pH 7.5, 37°C, recombinant enzyme
-
0.294
[histone H4]-N6-succinyl-L-lysine91
pH 7.5, 37°C, recombinant enzyme
-
0.000066
[protein]-N6-acetyl-L-lysine
mutant enzyme Y102A, at 8.0 pH and 25°C
0.000026
NAD+
mutant enzyme Y102A/R105I, with [protein]-N6-acetyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
0.000122
NAD+
mutant enzyme R105I, with [protein]-N6-acetyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
0.000274
NAD+
mutant enzyme Y102A, with [protein]-N6-succinyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
0.04
NAD+
wild type enzyme, with [protein]-N6-succinyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
0.052
[histone H3 K9 peptide]-N6-acetyl-L-lysine
-
pH 8.0, 37°C, mutant enzyme Y92F
-
0.059
[histone H3 K9 peptide]-N6-acetyl-L-lysine
-
pH 8.0, 37°C, mutant enzyme R95M
-
0.135
[histone H3 K9 peptide]-N6-acetyl-L-lysine
-
pH 8.0, 37°C, wild-type enzyme
-
0.000026
[protein]-N6-succinyl-L-lysine
mutant enzyme Y102A/R105I, at 8.0 pH and 25°C
0.000274
[protein]-N6-succinyl-L-lysine
mutant enzyme R105I, at 8.0 pH and 25°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.73
[histone H2A]-N6-succinyl-L-lysine95
pH 7.5, 37°C, recombinant enzyme
-
1.95
[histone H2A]-N6-succinyl-L-lysine9_(4-15)-A10G peptide
pH 7.5, 37°C, recombinant enzyme
-
4.81
[histone H2B]-N6-succinyl-L-lysine116
pH 7.5, 37°C, recombinant enzyme
-
3.18
[histone H2B]-N6-succinyl-L-lysine120
pH 7.5, 37°C, recombinant enzyme
-
3.15
[histone H2B]-N6-succinyl-L-lysine34
pH 7.5, 37°C, recombinant enzyme
-
2.94
[histone H3]-N6-succinyl-L-lysine122
pH 7.5, 37°C, recombinant enzyme
-
2.09
[histone H3]-N6-succinyl-L-lysine14
pH 7.5, 37°C, recombinant enzyme
-
1.78
[histone H3]-N6-succinyl-L-lysine14_(9-20)-A15G peptide
pH 7.5, 37°C, recombinant enzyme
-
2.86
[histone H3]-N6-succinyl-L-lysine56
pH 7.5, 37°C, recombinant enzyme
-
2.51
[histone H3]-N6-succinyl-L-lysine79
pH 7.5, 37°C, recombinant enzyme
-
4.35
[histone H3]-N6-succinyl-L-lysine9
pH 7.5, 37°C, recombinant enzyme
-
2.01
[histone H4]-N6-succinyl-L-lysine12
pH 7.5, 37°C, recombinant enzyme
-
1.7
[histone H4]-N6-succinyl-L-lysine31
pH 7.5, 37°C, recombinant enzyme
-
2.87
[histone H4]-N6-succinyl-L-lysine31_(26-37)-P32A peptide
pH 7.5, 37°C, recombinant enzyme
-
2.52
[histone H4]-N6-succinyl-L-lysine77
pH 7.5, 37°C, recombinant enzyme
-
2.89
[histone H4]-N6-succinyl-L-lysine91
pH 7.5, 37°C, recombinant enzyme
-
3
[histone H3 K9 peptide]-N6-acetyl-L-lysine
-
pH 8.0, 37°C, mutant enzyme R95M
-
3.5
[histone H3 K9 peptide]-N6-acetyl-L-lysine
-
pH 8.0, 37°C, mutant enzyme Y92F
-
8.9
[histone H3 K9 peptide]-N6-acetyl-L-lysine
-
pH 8.0, 37°C, wild-type enzyme
-
0.022
[histone H3 K9 peptide]-N6-succinyl-L-lysine
-
pH 8.0, 37°C, mutant enzyme R95M
-
0.067
[histone H3 K9 peptide]-N6-succinyl-L-lysine
-
pH 8.0, 37°C, mutant enzyme Y92F
-
2.8
[histone H3 K9 peptide]-N6-succinyl-L-lysine
-
pH 8.0, 37°C, wild-type enzyme
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0043
benzoyl-GVL(N6-(3-methyl-3-phenyl)succinyl)KEYGV-amide
pH 7.8, 37°C
0.0381
benzoyl-GVL(N6-(N-benzyloxycarbonyl-L-aspartyl))KEYGV-amide
pH 7.8, 37°C
0.0249
benzoyl-GVL(N6-(N-phthaloyl-DL-gamma-glutamyl))KEYGV-amide
pH 7.8, 37°C
0.0043
N-benzylglycyl-L-valyl-L-leucyl-N6-(3-carboxy-3-phenylbutanoyl)-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
pH 7.8, 37°C, recombinant enzyme
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.07256
(2S)-2-[(naphthalen-2-yl)sulfanyl]-4-oxo-4-[(3-phenylpropyl)amino]butanoic acid
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.124
(2S)-4-(benzylamino)-2-[(naphthalen-2-yl)sulfanyl]-4-oxobutanoic acid
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.09
(2S)-4-[3-(methylcarbamoyl)anilino]-2-[(naphthalen-2-yl)sulfanyl]-4-oxobutanoic acid
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.074
(2S)-4-[[(5S)-5-acetamido-6-amino-6-oxohexyl]amino]-2-[(naphthalen-2-yl)sulfanyl]-4-oxobutanoic acid
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.0195
(3E)-3-[(3,5-dibromo-4-hydroxyphenyl)methylidene]-5-iodo-1,3-dihydro-2H-indol-2-one
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.0559
(5E)-1-ethyl-5-(1H-indol-3-ylmethylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
pH 8.0, 37°C
0.027
(5E)-5-(1H-indol-3-ylmethylidene)-1-methyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
pH 8.0, 37°C
0.0673
(5E)-5-[4-(benzyloxy)benzylidene]-1-(prop-2-en-1-yl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
pH 8.0, 37°C
0.0129
(5E)-5-[4-(benzyloxy)benzylidene]-1-ethyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
pH 8.0, 37°C
0.0178
(5E)-5-[4-(benzyloxy)benzylidene]-1-methyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
pH 8.0, 37°C
0.0023
(5E)-5-[[5-(2,3-dichlorophenyl)furan-2-yl]methylidene]-1-(prop-2-en-1-yl)-2-sulfanylidene-1,3-diazinane-4,6-dione
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.0023
(5E)-5-[[5-(2,3-dichlorophenyl)furan-2-yl]methylidene]-1-(prop-2-en-1-yl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
pH 8.0, 37°C
0.001
(N6-thiosuccinyl)KSTGGKA
Homo sapiens
pH and temperature not specified in the publication
0.0001
1,8-dihydroxyanthracen-9(10H)-one
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.0056
4-[5-[2-cyano-3-(4-cyano-3-fluoroanilino)-3-oxopropyl]furan-2-yl]benzoic acid
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.0465
5-(1H-indol-3-ylmethylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
pH 8.0, 37°C
0.03
5-(biphenyl-4-ylmethylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
pH 8.0, 37°C
0.0166
5-[(1-benzyl-1H-indol-3-yl)methylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
pH 8.0, 37°C
0.0224
5-[(6-methoxynaphthalen-1-yl)methylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
pH 8.0, 37°C
0.0126
5-[4-(benzyloxy)benzylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
pH 8.0, 37°C
0.0394
5-[4-(propan-2-yl)benzylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
pH 8.0, 37°C
0.0124
5-[4-[(2-chlorobenzyl)oxy]-3-methoxybenzylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
pH 8.0, 37°C
0.0062
5-[4-[(4-bromobenzyl)oxy]benzylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
pH 8.0, 37°C
0.0126
5-[[4-(benzyloxy)phenyl]methylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.0036
5-[[5-(2,3-dichlorophenyl)furan-2-yl]methylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
pH 8.0, 37°C
0.04
Ac-AR(N6-thiosuccinyl)KST-NH2
Homo sapiens
pH and temperature not specified in the publication
0.025
Ac-RR(N6-thiosuccinyl)KRR-NH2
Homo sapiens
pH and temperature not specified in the publication
0.03
AR(N6-thiosuccinyl)KST
Homo sapiens
pH and temperature not specified in the publication
0.001
KQTAR(N6-thiosuccinyl)K
Homo sapiens
pH and temperature not specified in the publication
0.005
KQTAR(N6-thiosuccinyl)KSTGGKA
Homo sapiens
pH and temperature not specified in the publication
0.005
L-lysyl-L-glutaminyl-L-threonyl-L-alanyl-L-arginyl-N6-(3-carboxypropanethioyl)-L-lysyl-L-seryl-L-threonylglycylglycyl-L-lysyl-L-alanine
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.0075
N-([4-[(2S,5R,27S)-27-acetamido-8-[[(2R,3S)-1-amino-3-hydroxy-1-oxobutan-2-yl]carbamoyl]-2-(3-carbamimidamidopropyl)-3,6,14,21,28-pentaoxo-1,4,7,13,22-pentaazacyclooctacosan-5-yl]butyl]carbamothioyl)-beta-alanine
Homo sapiens
pH 8.0, 37°C
0.004
N-([4-[(3S,6S,16S)-6-(3-carbamimidamidopropyl)-16-carbamoyl-2,5,8,11-tetraoxo-1,4,7,12-tetraazacyclohexadecan-3-yl]butyl]carbamothioyl)-beta-alanine
Homo sapiens
pH 8.0, 37°C
0.0971
N-([4-[(3S,6S,17S)-17-carbamoyl-2,5,8,11-tetraoxo-6-propyl-1,4,7,12-tetraazacycloheptadecan-3-yl]butyl]carbamothioyl)-beta-alanine
Homo sapiens
pH 8.0, 37°C
0.0022
N-([4-[(3S,6S,17S)-6-(3-carbamimidamidopropyl)-17-carbamoyl-2,5,8,11-tetraoxo-1,4,7,12-tetraazacycloheptadecan-3-yl]butyl]carbamothioyl)-beta-alanine
Homo sapiens
pH 8.0, 37°C
0.0132
N-([4-[(3S,6S,18S)-6-(3-carbamimidamidopropyl)-18-carbamoyl-2,5,8,12-tetraoxo-1,4,7,13-tetraazacyclooctadecan-3-yl]butyl]carbamothioyl)-beta-alanine
Homo sapiens
pH 8.0, 37°C
0.0075
N-([4-[(3S,6S,9S)-9-acetamido-27-[[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]carbamoyl]-6-(3-carbamimidamidopropyl)-2,5,8,14,21-pentaoxo-1,4,7,13,22-pentaazacycloheptacosan-3-yl]butyl]carbamothioyl)-beta-alanine
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.0521
N-([4-[(5S,8S,11S)-5-(3-carbamimidamidopropyl)-11-carbamoyl-3,6,9,17-tetraoxo-4,7,10,16-tetraazabicyclo[17.2.2]tricosa-1(21),19,22-trien-8-yl]butyl]carbamothioyl)-beta-alanine
Homo sapiens
pH 8.0, 37°C
0.00035
N-acetyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(naphthalen-2-yl)sulfanyl]propanoyl]-L-lysyl-L-alaninamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.001075
N-acetyl-L-leucyl-N6-[3-carboxy-3-[(naphthalen-2-yl)sulfanyl]propanoyl]-L-lysyl-L-alaninamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.022803
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-(3-carboxy-3-[[2-(pyrazin-2-yl)ethyl]sulfanyl]propanoyl)-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.006966
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-(3-carboxy-3-[[2-(pyridin-2-yl)ethyl]sulfanyl]propanoyl)-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.013244
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-(3-carboxy-3-[[2-(pyridin-4-yl)ethyl]sulfanyl]propanoyl)-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.001122
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-(3-carboxy-4-phenylbutanoyl)-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000644
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-(benzylsulfanyl)-3-carboxypropanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.014
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-(cyclohexylsulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.001799
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-(phenylsulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.001148
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-([[3-(trifluoromethyl)phenyl]methyl]sulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.002203
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-([[4-(trifluoromethyl)phenyl]methyl]sulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.003388
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(2,3-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.002013
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(2,4-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.012503
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(2,6-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.003097
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(2-chlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000592
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(2-phenylethyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.001607
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(3,4-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.001259
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(3,4-dimethylphenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000647
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(3,5-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.001384
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(3-chlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.002061
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(3-phenylpropyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.001614
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(4-chlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.002196
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(naphthalen-1-yl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.00009
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(naphthalen-2-yl)sulfanyl]butanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.00181
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[(naphthalen-2-yl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000631
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[(2,4,6-trimethylphenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000432
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[(2,4-dichlorophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000352
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[(2-chlorophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.00078
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[(3,4-dichlorophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.002673
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[(3-nitrophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.001021
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[(4-chlorophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.001112
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[(4-methoxyphenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.0004027
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[(4-nitrophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000207
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[(naphthalen-1-yl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.018493
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-carboxy-3-[[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.001236
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R)-3-[[(4-tert-butylphenyl)methyl]sulfanyl]-3-carboxypropanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.009078
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3R-3-carboxy-3-[(3,4-dimethoxyphenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000336
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-(benzylsulfanyl)-3-carboxypropanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.004
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-(cyclohexylsulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000274
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-(phenylsulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.001125
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-([[3-(trifluoromethyl)phenyl]methyl]sulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000804
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-([[4-(trifluoromethyl)phenyl]methyl]sulfanyl)propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000715
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(2,3-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000177
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(2,4-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000295 - 0.001977
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(2,5-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
0.000577
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(2,6-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000857
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(2-chlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.002742
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(2-phenylethyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000046
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(3,4-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000326
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(3,4-dimethoxyphenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000046
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(3,4-dimethylphenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000086
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(3,5-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.00012
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(3-chlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.00113
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(3-phenylpropyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000102
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(4-chlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000095
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(naphthalen-1-yl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000059
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(naphthalen-2-yl)sulfanyl]butanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.00003
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(naphthalen-2-yl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.0052
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[(2,4,6-trimethylphenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000543
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[(2,4-dichlorophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000533
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[(2-chlorophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.00074
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[(3,4-dichlorophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.00271
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[(3-nitrophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000893
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[(4-chlorophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.001047
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[(4-methoxyphenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.003732
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[(4-nitrophenyl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000015
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[(naphthalen-1-yl)methyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.00875
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[[2-(3,5-dimethyl-1,2-oxazol-4-yl)ethyl]sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.000793
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-[[(4-tert-butylphenyl)methyl]sulfanyl]-3-carboxypropanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.04
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[3-[(naphthalen-2-yl)sulfanyl]butanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.04
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[3-[(naphthalen-2-yl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.0000191
N-[5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoyl]-L-threonyl-L-threonyl-L-alpha-aspartyl-L-serylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(naphthalen-2-yl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.0000911
N-[5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoyl]-L-threonyl-L-threonyl-L-alpha-aspartyl-L-serylglycyl-L-valyl-L-leucyl-N6-[3-carboxy-3-[(naphthalen-2-yl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.0931
N2-acetyl-L-arginyl-N6-[(2-carboxyethyl)carbamothioyl]-L-lysyl-N6-acetyl-L-lysinamide
Homo sapiens
pH 8.0, 37°C
0.01572
(2S)-4-(butylamino)-2-[(naphthalen-2-yl)sulfanyl]-4-oxobutanoic acid
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.154
(2S)-4-(butylamino)-2-[(naphthalen-2-yl)sulfanyl]-4-oxobutanoic acid
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.0195
3-(3,5-dibromo-4-hydroxybenzyliden)-5-iodo-1,3-dihydroindol-2-one
Homo sapiens
pH 7.5, temperature not specified in the publication, substrate: SKEYFS-(succinylLys)-QK
0.097
3-(3,5-dibromo-4-hydroxybenzyliden)-5-iodo-1,3-dihydroindol-2-one
Homo sapiens
pH 7.5, temperature not specified in the publication, substrate: FKRGVL-(acetylLys)-EYGVKV
0.0111
Isonicotinamide
Homo sapiens
wild type enzyme, with 0.05 mM NAD+, at 8.0 pH and 25°C
0.000295
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(2,5-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.001977
N-benzylglycylglycyl-L-valyl-L-leucyl-N6-[(3S)-3-carboxy-3-[(2,5-dichlorophenyl)sulfanyl]propanoyl]-L-lysyl-L-alpha-glutamyl-L-tyrosylglycyl-L-valinamide
Homo sapiens
pH 7.8, 37°C, recombinant enzyme
0.021
nicotinamide
Homo sapiens
pH 7.8, 37°C, substrate: benzoyl-RGVL(succK)EYGV-amide
0.0142
suramin
Homo sapiens
pH 7.5, temperature not specified in the publication, substrate: acetylated peptide derived from carbamoylphosphate synthetase 1 (CPS1)
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
7.8
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Escherichia coli W3110 / ATCC 27325
strain W3110 is a K12 derivative that is wild-type for chemotaxis
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brenda
strain W3110 is a K12 derivative that is wild-type for chemotaxis
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728857, 728962, 729138, 729372, 729547, 729801, 729885, 729993, 730024, 730161, 730205, 730245, 730474, 730706, 730713, 730922, 730964, 730974, 731010
SwissProt
brenda
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738843, 739445, 755788, 755970, 756010, 756427, 756522, 756680, 757175, 757350, 757400, 757590, 758247, 776863, 776943, 776985, 777265, 777320, 777423, 777554, 778071, 778258, 778416, 779357, 779416
SwissProt
brenda
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SwissProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
in the cerebellar cortex, SIRT5 can be found in Purkinje cells, and is mainly distributed in the cytoplasm, but is not markedly expressed in the molecular layer or granular layer cells
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SIRT5 and SIRT1/2 have opposite expression patterns and functions in macrophages, overview
brenda
SIRT5 is overexpressed in human non-small cell lung cancer cells, high expression of SIRT5 predicts poor survival
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additional information
SIRT5 expression is observed to localize strictly to the periportal hepatocytes
brenda
additional information
sirtuin 5 (SIRT5) is upregulated in patients with type 2 diabetes and in pancreatic beta cell lines
brenda
additional information
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sirtuin 5 (SIRT5) is upregulated in patients with type 2 diabetes and in pancreatic beta cell lines
brenda
additional information
the SIRT5 gene is widely expressed, but expression patterns of different isoforms vary in tissues, expression analysis, overview
brenda
additional information
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the SIRT5 gene is widely expressed, but expression patterns of different isoforms vary in tissues, expression analysis, overview
brenda
additional information
SIRT5 displays broad tissue distribution, with highest levels in brain, heart, liver, kidney, muscle, and testis
brenda
additional information
SIRT5 displays broad tissue distribution, with highest levels in brain, heart, liver, kidney, muscle, and testis
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
SIRT5 isoforms (i.e., SIRT5iso1 and SIRT5iso2) are encoded by the human SIRT5 gene. Their C-termini slightly differ from each other. Although both isoforms contain cleavable mitochondrial targeting signals at their N-termini,it is found that the cleaved SIRT5iso2 is localized mainly in mitochondria, whereas the cleaved SIRT5iso1 is localized in both mitochondria and cytoplasm. The cytoplasmic localization of cleaved SIRT5iso1 is dependent on the SIRT5iso1-specific C-terminus
brenda
SIRT5 isozyme 4 is mainly localized in the cytoplasm
brenda
mainly distributed in the cytoplasm of Purkinje cells
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SIRT5 is targeted to protein complexes on the inner mitochondrial membrane via affinity for cardiolipin
brenda
SIRT5 is targeted to protein complexes on the inner mitochondrial membrane via affinity for cardiolipin
brenda
Sirt5 can be translocated into the mitochondrial intermembrane space, but also into the matrix
brenda
SIRT5 isoforms (i.e., SIRT5iso1 and SIRT5iso2) are encoded by the human SIRT5 gene. Their C-termini slightly differ from each other. Although both isoforms contain cleavable mitochondrial targeting signals at their N-termini, it is found that the cleaved SIRT5iso2 is localized mainly in mitochondria, whereas the cleaved SIRT5iso1 is localized in both mitochondria and cytoplasm. The C-terminus of SIRT5iso2, which is rich in hydrophobic amino acid residues, functions as a mitochondrial membrane insertion signal
brenda
SIRT5 isozymes 1, 2 and 3 are mitochondria-localized. The full-length SIRT5 protein (SIRT5iso1) contains the N-terminal 36 amino acid mitochondrial localization signal (MLS) peptide
brenda
SIRT5 is present both mitochondrially and extramitochondrially
brenda
a very small amount of SIRT5 is detected in the nuclear fraction
brenda
additional information
although Sirt5 localizes mainly in the mitochondria, a slight amount of Sirt5 is detected in the nuclear fraction
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brenda
additional information
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although Sirt5 localizes mainly in the mitochondria, a slight amount of Sirt5 is detected in the nuclear fraction
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brenda
additional information
SIRT5 is predominantly a mitochondrial matrix protein, but a significant portion of SIRT5 localizes to the cytosol, peroxisomes, and nucleus as well. SIRT5 activity is non-redundant with other sirtuins in mitochondria, and likely elsewhere in the cell as well
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brenda
additional information
SIRT5 is predominantly a mitochondrial matrix protein, but a significant portion of SIRT5 localizes to the cytosol, peroxisomes, and nucleus as well. SIRT5 activity is non-redundant with other sirtuins in mitochondria, and likely elsewhere in the cell as well
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Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug target
evolution
malfunction
metabolism
physiological function
additional information
drug target
study provides a valuable target to improve osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) after many times of passages in vitro long-term passaged BM-MSCs exhibit upregulated SIRT5 expression, which leads to a decrease in UQCRC2 succinylation modification levels. This, in turn, enhances the activity of mitochondrial respiratory complex III and mitochondrial OXPHOS levels, impairs mitochondrial stability, and ultimately weakens the osteogenic differentiation capacity of BM-MSCs cells. Knockdown of SIRT5 can significantly reduce OXPHOS, maintain the normal function of mitochondria, and promote osteogenic differentiation of BM-MSCs even after many times of passages
drug target
SIRT5 is a promising biomarker for colorectal cancer because of its oncogenic role and SIRT5 has potential value for selective targeted therapy of colorectal cancer. SIRT5 may contribute to the development of new strategies for the treatment of gastric cancer. SIRT5 may function as a potential marker and drug target in clinical hepatocellular carcinoma diagnosis and therapy
drug target
reduction of SIRT5 protein expression and LDHA-K118su is a mechanism involved in prostate cancer progression, which could serve as a target to prevent castration-resistant prostate cancer progression for prostate cancer treatment
drug target
SIRT5 is a promising target in the design of activators or inhibitors that might act as therapeutics in many pathologies, including cancer, cardiovascular disorders, and neurodegeneration. Activating SIRT5 could be a promising strategy to target pancreatic ductal adenocarcinoma
drug target
SIRT5 inhibits glycolysis via catalyzing the desuccinylation of glycolytic enzyme glucose-6-phosphate isomerase, thereby repressing extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) cell proliferation and tumor growth. As SIRT5 serves as a tumor suppressor in ENKTL, it may be a promising molecular target in therapy strategy
drug target
SIRT5 inhibitors as potential chemical/pharmacological probes of SIRT5 and therapeutics for human diseases in which SIRT5 desuccinylase activity is upregulated
drug target
Sirt5 is a promising therapeutic target for addressing hyperglycemia and lipid metabolism abnormalities in type 2 diabetes mellitus
evolution
sirtuins, which are class III histone deacetylases (HDACs), are an evolutionarily conserved family of NAD-dependent lysine deacetylases that play important roles in the regulation of aging, tumorigenesis, energy metabolism and stress resistance
evolution
sirtuins (SIRTs) are proteins that possess nicotinxadamide-adenine dinucleotide-dependent deacetylase activity and belong to the histone deacetylase (HDAC) family, which consist of seven different subtypes in mammals (SIRT1-7)
evolution
mammals possess seven sirtuin family members (SIRT1-SIRT7), which display diverse subcellular localization patterns, catalytic activities, protein targets, and biological functions
evolution
sirtuins are a family of NAD+-dependent silent information regulator 2 (Sir2) enzymes that catalyze the removal of acyl groups from epsilon-N-amino groups of lysine residues in the proteome
evolution
sirtuins are a family of NAD+-dependent silent information regulator 2 (Sir2) enzymes that catalyze the removal of acyl groups from epsilon-N-amino groups of lysine residues in the proteome
evolution
SIRT5 gene encodes for four SIRT5 protein isoforms, namely SIRT5iso1, SIRT5iso2, SIRT5iso3, and SIRT5iso4
evolution
in mammals, the sirtuin family comprises seven members (SIRT1-7), which possess conserved NAD+-binding and catalytic domains, while their flanking N- and C-termini are distinct from one another, and contribute to differences in subcellular localization, enzymatic activity, and substrate specificity among sirtuin proteins. Phylogenetically, SIRT5 is distinct from other mammalian sirtuins, and belongs to the so-called class III sirtuin family, a family that includes mostly prokaryotic sirtuins. The human SIRT5 gene encodes two main SIRT5 isoforms, SIRT5iso1 and SIRT5iso2 comprising 310 amino acids and 299 amino acids respectively, which differ slightly from one other at their C-termini, two other human SIRT5 isoforms (SIRT5iso3 and SIRT5iso4) have been reported. SIRT5iso3 is identical to SIRT5iso1 except that it lacks an internal sequence of 18 amino acids, while in SIRT5iso4 the initial 108 amino acids of SIRT5iso1 are missing, including the mitochondrial localization sequence. SIRT5iso4 completely aligns with amino acids 109-310 of SIRT5iso1. SIRT5 polymorphisms may impact human lifespan. Presence of a single-nucleotide polymorphism (SNP) (rs9382222) in a conserved region of the SIRT5 promoter correlates with reduced SIRT5 mRNA expression levels in the anterior cingulate cortex (ACC) region of the brain in individuals with the CC genotype relative to individuals with the CT genotype. SNP rs2841505 is associated with slightly reduced lifespan in cohort members with a GG genotype compared to those with other genotypes. Another SIRT5 SNP, rs4712047, displays gender-specific impact on the lifespan, females with a GG genotype exhibited an increased lifespan compared to those with a GA or a AA genotype, whereas males with a GG genotype display decreased lifespan compared to males with the other genotypes. Association of SIRT5 SNP rs2253217 with human lifespan, cohort members with TT genotype live longer than those with TC or CC genotype
evolution
in mammals, the sirtuin family comprises seven members (SIRT1-7), which possess conserved NAD+-binding and catalytic domains, while their flanking N- and C-termini are distinct from one another, and contribute to differences in subcellular localization, enzymatic activity, and substrate specificity among sirtuin proteins. Phylogenetically, SIRT5 is distinct from other mammalian sirtuins, and belongs to the so-called class III sirtuin family, a family that includes mostly prokaryotic sirtuins. Mouse Sirt5 gene encodes a single protein of 310 amino acids, corresponding to human SIRT5 isoform 1
malfunction
deletion of Sirt5 in mice increases the level of succinylation on carbamoyl phosphate synthase 1
malfunction
SIRT5 knockdown represses lung cancer cell growth and transformation in vitro and in vivo. SIRT5 knockdown makes lung cancer cells more sensitive to drug (cis-diamminedichloroplatinum, 5-fluorouracil or bleomycin) treatment in vitro and in vivo. Nrf2, which is a core transcription factor for lung cancer growth and drug resistance, is a target of SIRT5
malfunction
SIRT5 knockdown in cardiomyocytes results in a marked reduction in cell viability, and a significant increase in the number of apoptotic cells
malfunction
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CobB knockout cells show slightly increased acetylation levels and succinylation levels relative to the wild type cells
malfunction
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RcsB protein isolated from a cobB deletion mutation strain is hyperacetylated
malfunction
-
acetyl-coenzyme A synthetase overproduced by the cobB deletion mutant strain contains acetyllysine at residue Lys609
malfunction
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knockdown or knockout of the enzyme leads to high levels of cellular reactive oxygen species. SIRT5 inactivation leads to the inhibition of isocitrate dehydrogenase 2 and glucose-6-phosphate dehydrogenase, thereby decreasing NADPH production, lowering GSH, impairing the ability to scavenge ROS, and increasing cellular susceptibility to oxidative stress
malfunction
SIRT5 knockout mice on the Sv129 background exhibit less browning capacity in subcutaneous white adipose tissue compared to controls and show apparent cold intolerance, suggesting that SIRT5 can modulate the browning process in vivo. Knockdown of SIRT5 impairs brown adipocyte differentiation of C3H10T1/2 multipotent mesenchymal cells and blocks adipogenic gene activation. Lipid accumulation and basal and uncoupled oxygen consumption rates are significantly reduced in SIRT5 knockdown cells. The expression levels of PPARgamma, PRDM16, and UCP1 are significantly augmented in the SIRT5 overexpression cells, which is consistent with the increased lipid accumulation. UCP1 expression is significantly increased in SIRT5 overexpression groups. Knockdown of SIRT5 reduces 2-oxoglutarate concentration and supplementation of 2-oxoglutarate partially rescues brown adipocyte differentiation in SIRT5 knockdown cells. Knockdown of SIRT5 results in increased H3K9me2 and H3K9me3 levels in the promoter regions of Ppargamma and Prdm16
malfunction
the SIRT5 deficiency mouse model shows that it is dispensable for metabolic homeostasis under normal conditions. The ob/ob-SIRT5 OE mice show decreased malonylation and succinylation, improved cellular glycolysis, suppressed gluconeogenesis, enhanced fatty acid oxidation, and attenuated hepatic steatosis. Hepatic overexpression of SIRT5 ameliorates the metabolic abnormalities of ob/obmice, probably through demalonylating and desuccinylating proteins in the main metabolic pathways. SIRT5 and related acylation might be potential targets for metabolic disorders
malfunction
SIRT5 deficiency decreases TLR-triggered inflammation in both acute and immunosuppressive phases of sepsis. Acetylation of p65 K310 is impaired in SIRT5-/- peritoneal macrophages upon TLR4 activation. The p65 overexpression-induced NF-kappaB reporter activity is significantly increased by SIRT5 overexpression, but impaired by SIRT1/2 overexpression in HEK-293T cells. Decreased expression of SIRT5 is found in cultured macrophages upon primary or second LPS stimulation
malfunction
SIRT5-KO mice have reduced survival upon transverse aortic constriction (TAC) compared with wild-type mice but exhibit no mortality when undergoing a sham control operation. The increased mortality with TAC is associated with increased pathological hypertrophy and with key abnormalities in both cardiac performance and ventricular compliance. An accelerated development of cardiac dysfunction in SIRT5KO mice in response to TAC, explaining increased mortality upon cardiac stress. Protein succinylation is increased in SIRT5-KO hearts and abundant on enzymes in oxidative metabolism. SIRT5-KO mouse phenotype, detailed overview
malfunction
SIRT5-deficient HEK-293 cells show defects in both Complex I- and Complex II-driven respiration. Humans with Complex II deficiency have mild lactic acidosis
malfunction
because these modifications by Sirt5 cover a broad range of pivotal protein substrates involved in cellular metabolism and metabolic energy homeostasis, aberrant activity of Sirt5 is considered to be a very critical factor for many human diseases, for example, cancer, Alzheimer's disease, and Parkinson's disease
malfunction
SIRT5-/- mice have mild lactic acidosis. SIRT5 deficiency does not affect the abundance of the respiratory chain complexes in liver mitochondria. Complex II and ATP synthase activities are reduced in SIRT5-/- liver
malfunction
depletion of SIRT5, a lysine desuccinylase, leads to increased ubiquitination of glutaminase. SIRT5 knockdown acts as a marker for subsequent ubiquitination at residue K158
malfunction
Sirt5-deficiency-mediated IL-1beta upregulation in LPS-stimulated macrophages, which can be attenuated by activation of PKM2 using TEPP-46. Sirt5-deficient mice are more susceptible to dextran sodium sulfate (DSS)-induced colitis, which is associated with Sirt5 deficiency prompted PKM2 hypersuccinylation and boosted IL-1beta production. Both activation of PKM2 and neutralization of IL-1beta in vivo confer protection against dextran sodium sulfate (DSS)-induced colitis in Sirt5-deficiency mice
malfunction
SIRT5 polymorphisms may impact human lifespan. Presence of a single-nucleotide polymorphism (SNP) (rs9382222) in a conserved region of the SIRT5 promoter correlates with reduced SIRT5 mRNA expression levels in the anterior cingulate cortex (ACC) region of the brain in individuals with the CC genotype relative to individuals with the CT genotype. SNP rs2841505 is associated with slightly reduced lifespan in cohort members with a GG genotype compared to those with other genotypes. Another SIRT5 SNP, rs4712047, displays gender-specific impact on the lifespan, females with a GG genotype exhibited an increased lifespan compared to those with a GA or a AA genotype, whereas males with a GG genotype display decreased lifespan compared to males with the other genotypes. Association of SIRT5 SNP rs2253217 with human lifespan, cohort members with TT genotype live longer than those with TC or CC genotype. In addition to mitochondrial proteins, a large number of cytosolic and nuclear proteins exhibit increased succinylation, malonylation, and glutarylation upon SIRT5 deletion
malfunction
in addition to mitochondrial proteins, a large number of cytosolic and nuclear proteins exhibit increased succinylation, malonylation, and glutarylation upon SIRT5 deletion. Despite the broad expression and unique activity profile of SIRT5, which is non-redundant with other mitochondrial sirtuins, Sirt5 knockout (KO) mice display no strong phenotypes or major metabolic abnormalities, and germline ablation of Sirt5 is well tolerated in mice under basal, unstressed conditions. Sirt5 KO mice on the C57BL/6 background are born at a sub-Mendelian ratio, an effect not observed in Sirt5 KO 129/J background animals. Sirt5 ablation in mice causes a dramatic increase of Ksucc, Kmal, and Kglu levels, globally across multiple tissues and embryonic fibroblasts, while it has very little impact on Kac levels
malfunction
deficiency of SIRT5 reduces the innate inflammatory response of macrophages
malfunction
SIRT5 depletion in PC-3 cells is associated with increased invasiveness
malfunction
-
deletion of SIRT5 results in hypersuccinylation of detoxification-related enzymes, and significant reduction in NADPH:NADP+ and GSH:GSSG ratios, disrupting redox balance and impeding invasive growth
malfunction
SIRT5 knockdown inhibits the improvement of mitochondrial function in palmitic acid-induced HepG2 cells by metformin hydrochloride
malfunction
-
the SIRT5 deficiency mouse model shows that it is dispensable for metabolic homeostasis under normal conditions. The ob/ob-SIRT5 OE mice show decreased malonylation and succinylation, improved cellular glycolysis, suppressed gluconeogenesis, enhanced fatty acid oxidation, and attenuated hepatic steatosis. Hepatic overexpression of SIRT5 ameliorates the metabolic abnormalities of ob/obmice, probably through demalonylating and desuccinylating proteins in the main metabolic pathways. SIRT5 and related acylation might be potential targets for metabolic disorders
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metabolism
SIRT5 plays a pivotal role in ammonia detoxification and disposal by activating carbamoyl phosphate synthetase 1 an enzyme, catalyzing the initial step of the urea cycle for ammonia detoxification and disposal
metabolism
human SIRT5 potentially controls various primate-specific functions via two isoforms with different intracellular localizations or stabilities
metabolism
SIRT5 is a protein responsible for growth and drug resistance in human non-small cell lung cancer cells
metabolism
the enzyme is involved in regulation of mitochondrial energy metabolism
metabolism
SIRT5 is involved in the regulation of oxidative stress induced apoptosis in cardiomyocytes
metabolism
SIRT5 deacetylates carbamoyl phosphate synthetase 1 (CPS1), an enzyme which is the first and rate-limiting step of urea cycle. Deacetylation of CPS1 by SIRT5 results in activation of CPS1 enzymatic activity
metabolism
SIRT5 has an emerging role in the metabolic adaptation to fasting, high protein diet and calorie restriction
metabolism
because ammonia generated during fasting is toxic, SIRT5 might play a protective role by converting ammonia to non-toxic urea through deacetylation and activation of carbamoyl phosphate synthase 1
metabolism
reversible Nepsilon-Lys acetylation of transcription factors is a mode of regulation of gene expression used by all cells
metabolism
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the Gcn5-like acetyltransferase YfiQ and the sirtuin deacetylase CobB play crucial roles in the transcription regulation of the periplasmic stress-responsive promoter cpxP when cells of Escherichia coli grow in the presence of glucose, an environment that induces protein acetylation
metabolism
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overexpression of CobB reduces the 6fold glucose-dependent induction to a more modest 3fold induction
metabolism
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sirtuin deacetylase CobB deficiency leads to both site-specific and global changes in protein acetylation stoichiometry, affecting central metabolism
metabolism
SIRT5 regulates brown adipogenic gene activation at least partly through an indirect effect on histone modifications, linkage between epigenetics and cell differentiation. SIRT5 is implicated in the urea cycle by activating carbamoyl phosphate synthetase 1. SIRT5 modifies lysine succinylation, malonylation, and glutarylation both inside and outside of the mitochondria and impacts multiple enzymes involved in diverse mitochondrial metabolic pathways. SIRT5 has crucial effects on cellular metabolite flux
metabolism
protein malonylation and succinylation lysine sites are identified by immunoprecipitation coupled lipid chromatography-tandem mass spectrometry (LC-MS/MS) methods. A total of 955 malonylation sites on 434 proteins and 1377 succinylation sites on 429 proteins were identified and quantitated. Malonylation is the major SIRT5 target in the glycolysis/gluconeogenesis pathway, whereas succinylation is the preferred SIRT5 target in the oxidative phosphorylation pathway. Identification, quantification, and analysis of malonylome and succinylome
metabolism
function of sirtuin family members in the inflammatory responses, overview. SIRT5 and SIRT1/2 have opposite expression patterns and functions in macrophages. Cytoplasmic SIRT5 counteracts the inhibitory effects of SIRT2 and enhances the innate inflammatory responses in macrophages and even in endotoxin-tolerant macrophages by promoting acetylation of p65 and activation of NF-kappaB pathway. Mechanistically, SIRT5 competes with SIRT2 to interact with NF-kappaB p65, in a deacetylase activity-independent way, to block the deacetylation of p65 by SIRT2, which consequently leads to increased acetylation of p65 and the activation of NF-kB pathway and its downstream cytokines
metabolism
SIRT5-mediated desuccinylation of ubiquinol-cytochrome C reductase core protein 2 (UQCRC2) at the site of Lys250 promotes UQCRC2 translocation from cytoplasm to mitochondria, which enhanced the activity of mitochondrial respiratory complex III. It further increases mtROS, accelerates cellular senescence and inhibits the osteogenic differentiation of bone marrow mesenchymal stem cells
metabolism
SIRT5 is closely related to some diseases such as cancer and neurodegenerative diseases
metabolism
sirtuin 5 is a cancer metastatic stimulator in aggressive prostate cancer
metabolism
metformin hydrochloride ameliorates hepatic glucose and lipid metabolic disorders as well as mitochondrial dysfunction in high-fat diet-fed mice through SIRT5-mediated desuccinylation of enhanced trifunctional enzyme subunit-alpha (ECHA)
metabolism
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protein malonylation and succinylation lysine sites are identified by immunoprecipitation coupled lipid chromatography-tandem mass spectrometry (LC-MS/MS) methods. A total of 955 malonylation sites on 434 proteins and 1377 succinylation sites on 429 proteins were identified and quantitated. Malonylation is the major SIRT5 target in the glycolysis/gluconeogenesis pathway, whereas succinylation is the preferred SIRT5 target in the oxidative phosphorylation pathway. Identification, quantification, and analysis of malonylome and succinylome
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physiological function
protein lysine succinylation may represent a posttranslational modification that can be reversed by Sirt5
physiological function
SIRT5 is a central regulator of Lys succinylation in mammalian cells
physiological function
SIRT5 overexpression increases ATP synthesis and oxygen consumption in HepG2 cells, but does not affect mitochondrial biogenesis
physiological function
SIRT5 is involved in influencing oocyte quality and in-vitro-fertilisation outcomes
physiological function
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the enzyme regulates chemotaxis of Escherichia coli by deacetylating CheY
physiological function
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acetylation of the response regulator RcsB controls transcription from the small RNA promoter rprA
physiological function
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deacetylation by CobB activates the acetyl-coenzyme A synthetase
physiological function
the enzyme regulates protein function in diverse and often essential cellular processes, most notably translation. CobB is the predominate deacetylase in Escherichia coli loop or a helix that protrudes into the solution and thus in position to be an easily accessible target
physiological function
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the enzyme prevents cigarette smoke extract-induced apoptosis in lung epithelial cells via deacetylation of FOXO3
physiological function
adipose tissue plays a vital role in metabolic regulation. SIRT5 regulates brown adipocyte differentiation and browning of subcutaneous white adipose tissue. SIRT5 modifies lysine succinylation, malonylation, and glutarylation both inside and outside of the mitochondria. SIRT5 can desuccinylate and deglutarylate IDH2 and G6PD, respectively, thereby activating both enzymes to maintain cellular NADPH homeostasis and redox potential during oxidative stress. SIRT5 is essential for brown adipocyte differentiation in vitro and has an impact on browning of subcutaneous adipose tissue in vivo. SIRT5 may play an important role in adaptive thermogenesis of brown/beige adipocytes
physiological function
Sirtuin 5 (SIRT5) is a NAD+-dependent lysine deacylase. SIRT5 deacylates metabolism-related proteins and attenuates hepatic steatosis in obese ob/ob mice
physiological function
SIRT5 enhances acetylation (K310) of NF-kappaB p65 in response to innate stimuli. SIRT5 enhances acetylation of p65 by blocking p65 interaction of SIRT2. Endogenous SIRT5 interacts with p65 in the cytoplasm of macrophages. SIRT5 rescues hypo-inflammatory response in endotoxin-tolerant macrophages
physiological function
sirtuin 5 (SIRT5) is upregulated in patients with type 2 diabetes. Elevated SIRT5 expression is positively associated with age and blood glucose levels, and negatively associated with pancreatic and duodenal homeobox 1 (PDX1) expression. SIRT5 regulates pancreatic beta cell proliferation and insulin secretion in type 2 diabetes. SIRT5 suppresses the proliferation of pancreatic beta cells in vitro. While SIRT5 possesses weak deacetylase activity, it catalyzes the modification of acidic lysine residues by glutaryxadlation, succinylation, and malonylation well. PDX1 is transcriptionally regulated by SIRT5 via H4K16 deacetylation. PDX1 is involved in SIRT5-mediated insulin secretion and pancreatic beta cell proliferation
physiological function
in mitochondria, the sirtuin SIRT5 is an NAD+-dependent protein deacylase controls several metabolic pathways. A wide range of SIRT5 targets have been identified. SIRT5 functions in organismal metabolic homeostasis. SIRT5 plays a role in cardiac stress responses
physiological function
sirtuins are protein deacylases that regulate metabolism and stress responses and are implicated in aging-related diseases
physiological function
SIRT5 is a lysine desuccinylase known to regulate mitochondrial fatty acid oxidation and the urea cycle. SIRT5 binds to cardiolipin and regulates the electron transport chain. SIRT5 is targeted to protein complexes on the inner mitochondrial membrane via affinity for cardiolipin to promote respiratory chain function. SIRT5 restores membrane binding of very-long-chain acyl-CoA dehydrogenase (VLCAD). SIRT5 electrostatically binds to cardiolipin and desuccinylates mitochondrial inner membrane proteins including multiple subunits of all four electron transport chain (ETC) complexes and ATP synthase. SIRT5 counteracts succinylation of mitochondrial membrane proteins, overview
physiological function
Sirt5 has only weak deacetylation, but has robust desuccinylation, demalonylation, and deglutarylation activities in vitro and in vivo. Modifications by Sirt5 cover a broad range of pivotal protein substrates involved in cellular metabolism and metabolic energy homeostasis
physiological function
SIRT5 is a lysine desuccinylase known to regulate mitochondrial fatty acid oxidation and the urea cycle. SIRT5 binds to cardiolipin and regulates the electron transport chain. SIRT5 is targeted to protein complexes on the inner mitochondrial membrane via affinity for cardiolipin to promote respiratory chain function. Three-dimensional modeling of Complex II suggests that several SIRT5-targeted lysine residues lie at the protein-lipid interface of succinate dehydrogenase subunit B. Succinylation at these sites may disrupt Complex II subunit-subunit interactions and electron transfer. SIRT5 restores membrane binding of very-long-chain acyl-CoA dehydrogenase (VLCAD). SIRT5 electrostatically binds to cardiolipin and desuccinylates mitochondrial inner membrane proteins including multiple subunits of all four electron transport chain (ETC) complexes and ATP synthase. SIRT5 counteracts succinylation of mitochondrial membrane proteins, overview
physiological function
SIRT5, a mitochondrial NAD+-dependent lysine deacylase, plays a key role in stabilizing glutaminase. In transformed cells, SIRT5 regulates glutamine metabolism by desuccinylating glutaminase and thereby protecting it from ubiquitin-mediated degradation. SIRT5 is upregulated during cellular transformation and supports proliferation and tumorigenesis. SIRT5 is upregulated during oncogenic transformation and stabilizes glutaminase, an enzyme with important functions in cancer-cell metabolic reprogramming. Elevated SIRT5 expression in human breast tumors correlates with poor patient prognosis. Role for SIRT5 in metabolic reprogramming and mammary tumorigenesis. SIRT5 supports proliferation and anchorage-independent growth
physiological function
sirtuins are NAD+-dependent enzymes that regulate diverse cellular processes, thereby maintaining metabolic homeostasis and genomic integrity.Sirtuin-family deacylases promote health and longevity in mammals. The sirtuin SIRT5 localizes predominantly to the mitochondrial matrix. SIRT5 preferentially removes negatively charged modifications from its target lysines: succinylation, malonylation, and glutarylation. It regulates protein substrates involved in glucose oxidation, ketone body formation, ammonia detoxification, fatty acid oxidation, and ROS management
physiological function
potential role of isozyme SIRT5iso2 in neuron system
physiological function
human sirtuin 5 (Sirt5) catalyzes the sequence-selective desuccinylation of numerous histone succinyl sites. Compared with Sirt1, 2, 3, and 6, enzyme Sirt5 exhibits relatively weak deacetylation activity but can more efficiently remove negatively charged modifications, such as malonylation, glutarylation, and especially succinylation, from lysine residues. Sirt5 is considered a desuccinylase
physiological function
SIRT5 plays an important role in inhibiting inflammation. SIRT5 suppresses the pro-inflammatory response in macrophages at least in part by regulating PKM2 succinylation, activity, and function. SIRT5 desuccinylates and activates pyruvate kinase M2 (PKM2) to block macrophage IL-1beta production and to prevent DSS-induced colitis in mice. Lys311 is a key succinylated site in the regulation of PKM2 activity. SIRT5-regulated hypersuccinylation inhibits the pyruvate kinase activity of PKM2 by promoting its tetramer-to-dimer transition. A succinylation-mimetic PKM2 K311E mutation promotes nuclear accumulation and increases protein kinase activity. SIRT5-dependent succinylation promotes PKM2 entry into nucleus, where a complex of PKM2-HIF1alpha is formed at the promoter of interleukin-1beta gene in LPS-stimulated macrophages. SIRT5-dependent succinylation promotes PKM2 dimerization and increases its protein kinase activity
physiological function
role of SIRT5 as a significant regulator of cellular homeostasis in a context- and cell-type specific manner. SIRT5 regulates protein substrates involved in glycolysis, TCA cycle, fatty acid oxidation, electron transport chain, ketone body formation, nitrogenous waste management, and ROS detoxification, among other processes. SIRT5 plays pivotal roles in cardiac physiology and stress responses, and is involved in the regulation of numerous aspects of myocardial energy metabolism. SIRT5 is implicated in neoplasia, as both a tumor promoter and suppressor in a context-specific manner, and may serve a protective function in the setting of neurodegenerative disorders. SIRT5 displays a unique affinity for negatively charged acyl lysine modifications, and performs protein desuccinylation, demalonylation, and deglutarylation reactions. SIRT5 is selective only for 3-5 carbon chains acidic acyl modifications, and displays no detectable activity against either an acetyl modification, a neutral 2 carbon group, or an adipoyl, a 6-carbon acidic modification. SIRT5 regulates glycolysis, the TCA cycle and the electron transport chain. It plays a role in fatty acid beta-oxidation and promotes reactive oxygen species (ROS) detoxification. SIRT5 contributes to nitrogenous waste management and maintains cardiac homeostasis under stress. SIRT5 plays Janus-faced roles in cancer, it acts as a tumor promoter and s tumor suppressor. Role of SIRT5 in the pathogenesis of neurodegenerative disorders. Physiological function of SIRT5 , detailed overview
physiological function
role of SIRT5 as a significant regulator of cellular homeostasis in a context- and cell-type specific manner. SIRT5 regulates protein substrates involved in glycolysis, TCA cycle, fatty acid oxidation, electron transport chain, ketone body formation, nitrogenous waste management, and ROS detoxification, among other processes. SIRT5 plays pivotal roles in cardiac physiology and stress responses, and is involved in the regulation of numerous aspects of myocardial energy metabolism. SIRT5 is implicated in neoplasia, as both a tumor promoter and suppressor in a context-specific manner, and may serve a protective function in the setting of neurodegenerative disorders. SIRT5 displays a unique affinity for negatively charged acyl lysine modifications, and performs protein desuccinylation, demalonylation, and deglutarylation reactions. SIRT5 is selective only for 3-5 carbon chains acidic acyl modifications, and displays no detectable activity against either an acetyl modification, a neutral 2 carbon group, or an adipoyl, a 6-carbon acidic modification. SIRT5 regulates glycolysis, the TCA cycle and the electron transport chain. It plays a role in fatty acid beta-oxidation and promotes reactive oxygen species (ROS) detoxification. SIRT5 contributes to nitrogenous waste management and maintains cardiac homeostasis under stress. SIRT5 plays Janus-faced roles in cancer, it acts as a tumor promoter and s tumor suppressor. Role of SIRT5 in the pathogenesis of neurodegenerative disorders. Physiological function of SIRT5, detailed overview
physiological function
SIRT5 directly interacts to desuccinylate histidine triad nucleotide binding protein 1 and exerts antileukemic effects
physiological function
desuccinylation of TBK1 by SIRT5 regulates inflammatory response of macrophages in sepsis
physiological function
sirtuin 5 (SIRT5) expression is associated with biological pathways such as oxidative phosphorylation, cellular senescence, and inhibition of osteogenic differentiation
physiological function
SIRT5 regulates glycolysis, the TCA cycle, and the electron transport chain. SIRT5 promotes fatty acid beta-oxidation and ketone body production
physiological function
SIRT5 exhibits significant regulatory roles in tumor biology. SIRT5 plays a pivotal role in cellular energy metabolism and homeostasis. SIRT5-mediated desuccinylation of 2-oxoglutarate dehydrogenase (OGDH) inhibits the OGDH complex's activity, leading to reduced mitochondrial membrane potential, decreased ATP production, increased ROS levels, and altered NADP/NADPH ratios, ultimately suppressing gastric cancer progression
physiological function
SIRT5 is involved in cell metabolism, including glycolysis, tricarboxylic acid cycle, fatty acid oxidation, nitrogen metabolism, pentose phosphate pathway, antioxidant defense, and apoptosis. Although SIRT5 plays important regulatory roles in tumor progression in the liver and gastric cancer
physiological function
a SIRT5-dependent mechanism modulates intracellular NADPH homeostasis to attenuate ammonia-induced oxidative stress by enhancing isocitrate dehydrogenase 2 enzymatic activity. SIRT5 desuccinylates isocitrate dehydrogenase 2 to enhance its activity, resulting in increased NADPH production
physiological function
SIRT5 is involved in different processes, including the maintenance of genomic stability, metabolism, and tumor microenvironment regulation. SIRT5 plays a dichotomous role, since it either suppresses or promotes cancer initiation or progression depending on various factors such as tissue or cell type and transformation stage. This is a consequence, at least in part, of the SIRT5-mediated regulation of ATP production and oxidative stress. ROS detoxification may be beneficial in healthy cells to avoid DNA damage and prevent tumorigenesis. On the other hand, the same mechanism protects tumor cells from apoptosis, supports cell proliferation, and may reduce the susceptibility to genotoxic chemotherapeutics
physiological function
-
the desuccinylase is important for virulence via adaptation to host oxidative stress. Importance of Sirt5-mediated desuccinylation in controlling fungal process required for detoxifying host ROS during Pyricularia oryzae infection. Sirt5 desuccinylates thioredoxin Trx2 and glutathione peroxidase Hyr1 to activate their enzyme activity, likely by affecting proper folding
physiological function
SIRT5 acts as a brake to orchestrate antiviral innate immunity
physiological function
SIRT5 inhibits glycolysis via catalyzing the desuccinylation of glycolytic enzyme glucose-6-phosphate isomerase, thereby repressing extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) cell proliferation and tumor growth. As SIRT5 serves as a tumor suppressor in ENKTL, it may be a promising molecular target in therapy strategy
physiological function
SIRT5 regulates glucose metabolism. SIRT5 is involved in insulin sensitivity
physiological function
SIRT5 inhibits glycolysis via catalyzing the desuccinylation of glycolytic enzyme glucose-6-phosphate isomerase, thereby repressing extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) cell proliferation and tumor growth. As SIRT5 serves as a tumor suppressor in ENKTL, it may be a promising molecular target in therapy strategy
physiological function
SIRT5 promotes malignant advancement of chordoma by regulating the desuccinylation of c-myc
physiological function
SIRT5 promotes malignant advancement of chordoma by regulating the desuccinylation of c-myc
physiological function
Escherichia coli W3110 / ATCC 27325
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the enzyme regulates chemotaxis of Escherichia coli by deacetylating CheY
-
physiological function
-
Sirtuin 5 (SIRT5) is a NAD+-dependent lysine deacylase. SIRT5 deacylates metabolism-related proteins and attenuates hepatic steatosis in obese ob/ob mice
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additional information
the mitochondrial processing peptidase cleavage site of SIRT5 leaves an amphipathic helix on the mature protein at the extreme N-terminus. This N-terminal amphipathic helix has three positively charged residues that orient into the solvent as seen in the SIRT5 crystal structure These positively charged residues might confer cardiolipin binding to SIRT5, similar to the amphipathic helix previously identified in very-long-chain acyl-CoA dehydrogenase (VLCAD)
additional information
-
the mitochondrial processing peptidase cleavage site of SIRT5 leaves an amphipathic helix on the mature protein at the extreme N-terminus. This N-terminal amphipathic helix has three positively charged residues that orient into the solvent as seen in the SIRT5 crystal structure These positively charged residues might confer cardiolipin binding to SIRT5, similar to the amphipathic helix previously identified in very-long-chain acyl-CoA dehydrogenase (VLCAD)
additional information
the mitochondrial processing peptidase cleavage site of SIRT5 leaves an amphipathic helix on the mature protein at the extreme N terminus. This N-terminal amphipathic helix has three positively charged residues that orient into the solvent as seen in the SIRT5 crystal structure These positively charged residues might confer cardiolipin binding to SIRT5, similar to the amphipathic helix previously identified in very-long-chain acyl-CoA dehydrogenase (VLCAD)
additional information
-
the mitochondrial processing peptidase cleavage site of SIRT5 leaves an amphipathic helix on the mature protein at the extreme N terminus. This N-terminal amphipathic helix has three positively charged residues that orient into the solvent as seen in the SIRT5 crystal structure These positively charged residues might confer cardiolipin binding to SIRT5, similar to the amphipathic helix previously identified in very-long-chain acyl-CoA dehydrogenase (VLCAD)
additional information
molecular mechanism underlying the sequence-selective desuccinylase activity of Sirt5, overview. Human Sirt5 is a ubiquitous desuccinylase that catalyzes the desuccinylation of diverse histone succinyl sites with sequence selectivity. Among the 13 identified sites, H2BK116su is the most favorable Sirt5 substrate, with H4K12su showing the lowest catalytic efficiency and no activity observed in the presence of H4K31su
additional information
-
molecular mechanism underlying the sequence-selective desuccinylase activity of Sirt5, overview. Human Sirt5 is a ubiquitous desuccinylase that catalyzes the desuccinylation of diverse histone succinyl sites with sequence selectivity. Among the 13 identified sites, H2BK116su is the most favorable Sirt5 substrate, with H4K12su showing the lowest catalytic efficiency and no activity observed in the presence of H4K31su
additional information
lysine succinylation (Ksucc), malonylation (Kmal), and glutarylation (Kglu), derived from succinyl-CoA, malonyl-CoA, and glutaryl-CoA respectively, have emerged as functionally important modifications, but most likely have distinct functions from Kac in regulating metabolism and other cellular processes. The presence of succinyl, malonyl, or glutaryl moiety confers upon a modified lysine residue a negative charge at physiological pH. SIRT5 preferentially catalyzes the removal of these negatively charged acidic modifications, thereby functioning as the dominant cellular desuccinylase, demalonylase, and deglutarylase. Compared to other sirtuins, SIRT5 possess a larger acyl binding pocket, able to accommodate these acyl modifications, which are bulkier than an acetyl group. The presence of alanine (Ala86), arginine (Arg105), and tyrosine (Tyr102) residues in the catalytic pocket of SIRT5 appears to be responsible for its specificity for negatively charged acyl groups
additional information
lysine succinylation (Ksucc), malonylation (Kmal), and glutarylation (Kglu), derived from succinyl-CoA, malonyl-CoA, and glutaryl-CoA respectively, have emerged as functionally important modifications, but most likely have distinct functions from Kac in regulating metabolism and other cellular processes. The presence of succinyl, malonyl, or glutaryl moiety confers upon a modified lysine residue a negative charge at physiological pH. SIRT5 preferentially catalyzes the removal of these negatively charged acidic modifications, thereby functioning as the dominant cellular desuccinylase, demalonylase, and deglutarylase. Compared to other sirtuins, SIRT5 possess a larger acyl binding pocket, able to accommodate these acyl modifications, which are bulkier than an acetyl group. The presence of alanine (Ala86), arginine (Arg105), and tyrosine (Tyr102) residues in the catalytic pocket of SIRT5 appears to be responsible for its specificity for negatively charged acyl groups
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). NPD1_ARCFU
Archaeoglobus fulgidus (strain ATCC 49558 / DSM 4304 / JCM 9628 / NBRC 100126 / VC-16)
245
0
27143
Swiss-Prot
-
NPD_ECOLI
Escherichia coli (strain K12)
279
0
31464
Swiss-Prot
Secretory Pathway (Reliability: 2)
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
the full-length SIRT5 protein (SIRT5iso1) contains the N-terminal 36 amino acid mitochondrial localization signal peptide and the remaining NAD+-dependent deacylase domain
additional information
-
the full-length SIRT5 protein (SIRT5iso1) contains the N-terminal 36 amino acid mitochondrial localization signal peptide and the remaining NAD+-dependent deacylase domain
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method at 4°C, crystal structure of wild-type enzyme, mutant enzyme S24A, mutant enzyme H80N, mutant enzyme F159A, and triple Sir2 mutant (D102G/F159A/R170A)
vapor diffusion at 20°C, crystal structure of the enzyme bound to KGLGKGGA(N6-succinyl)KRHRKW
purified recombinant detagged enzyme in complex with peptide inhibitors 2 and 15, sitting drop vapor diffusion method, mixing of 10 mg/ml protein with 1 mM inhibitor, crystallization in 0.002 ml of reservoir solution containing 0.1 M HEPES, pH 7.5, and 20% PEG 3350, 20°C, 2-4 days, X-ray diffraction structure determination and analysis at 2.4 A resolution, molecular replacement with search model PDB 4UTV and modeling
crystals of native and selenomethionine-derivatized cobB are grown at room temperature using the hanging-drop, vapor-diffusion method. The crystal structure of the Escherichia coli cobB core domain (residues 40274) in complex with an 11-residue peptide containing residues 1219 of histone H4 and acetylated at lysine 16 is determined by a combination of Zn2+ and Se multiwavelength anomalous diffraction to 1.96 A resolution
crystal structure of Sirt5 in complex with a thioacetyl peptide is obtained, The corresponding acetyl peptide could not be crystallized with Sirt5
crystal structure of Sirt5 in complex with fluor-de-Lys peptide and resveratrol and crystal structure of Sirt5 in complex with fluor-de-Lys peptide and piceatannol
crystal structures of a binary complex of SIRT5 with an H3K9 succinyl peptide and a binary complex of SIRT5 with a bicyclic intermediate obtained by incubating SIRT5-H3K9 thiosuccinyl peptide co-crystals with NAD+
hanging drop vapor diffusion method at 18°C. X-ray crystal structures of the ternary complex of SIRT5 bound to a peptide substrate and carba-NAD+ (an unreactive NAD+ analogue)
hanging drop vapor-diffusion method at 20°C. Crystal structures of SIRT5 in complex with ADP-ribose, and crystal structures of SIRT5 bound to suramin
purified recombinant enzyme SIRT5 in complex with succinylated histones, crystals of Sirt5-H4K122su and Sirt5-H2AK95su complexes are obtained from 0.1 M sodium cacodylate, pH 5.5, and 25% w/v PEG 4000 at 22°C. Sirt5-H4K91su complex is crystallized from 0.1 M Bis-Tris, pH 5.5, and 25% w/v PEG 3350, and Sirt5-H2BK120su complex is grown in 0.2 M sodium acetate trihydrate, 0.1 M sodium cacodylate trihydrate, pH 6.5, and 30% w/v PEG 8000, X-ray diffraction structure determination and analysis at 1.70-2.30 A resolution, molecular replacement using the structures PDB ID 3RIY as a searching model
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D101N
the decreased NAD-dependent deacetylase activity for the mutant proteins is at least partly due to reduced binding affinities for NAD+
F159A
the Km value of the mutant enzyme is twice that of wild type enzyme, whereas the kcat is 5fold less. In the F159A mutant, two water molecules occupy the position of the Phe159 ring
H80N
mutant retains about 60% of the NAD binding ability of wild type Sir2
S24A
the decreased NAD-dependent deacetylase activity for the mutant proteins is at least partly due to reduced binding affinities for NAD+
R95M
-
desuccinylation decreases about 100fold, deacetylation decreases about 3fold
Y92F
-
desuccinylation decreases about 42fold, deacetylation decreases about 3fold
H158M
catalytic efficiency (kcat/Km) of the mutant decreases to 0.0021 times that of the wild-type SIRT5
H158Y
N141V
catalytic efficiency (kcat/Km) of the mutant decreases to 0.0038 times that of the wild-type SIRT5
Q140L
catalytic efficiency (kcat/Km) of the mutant decreases to 0.02 times that of the wild-type SIRT5
R105L
Y102A
the mutant enzyme catalyzes both deacetylation and desuccinylation reactions with comparable efficiencies
Y102A/R105I
the mutant enzyme favores the deacetylase reaction over the desuccinylation reaction
H158Y
additional information
H158Y
site-directed mutagenesis, catalytically inactive mutant, method, overview
R105L
mutant retains wild-type deacetylation activity and partially gains Sirt3-like nicotinamide sensitivity (IC50: 0.189 mM)
R105L
the mutant enzyme favores the deacetylase reaction over the desuccinylation reaction
H158Y
site-directed mutagenesis, like the wild-type enzyme, mutant SIRT5-H158Y overexpression significantly increases secondary LPS stimulation-induced interleukin-6 and TNF-alpha production in RAW264.7 cells
additional information
SIRT5 ectopic expression downregulates the expression of pancreatic and duodenal homeobox 1 (PDX1) and the inhibition of SIRT5 upregulated PDX1 expression. SIRT5 knockout using small interfering RNA targeting sirtuin 5
additional information
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SIRT5 ectopic expression downregulates the expression of pancreatic and duodenal homeobox 1 (PDX1) and the inhibition of SIRT5 upregulated PDX1 expression. SIRT5 knockout using small interfering RNA targeting sirtuin 5
additional information
CRISPR (clustered regularly interspaced short palindromic repeats) is used to delete SIRT5 in human cell line HEK-293
additional information
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CRISPR (clustered regularly interspaced short palindromic repeats) is used to delete SIRT5 in human cell line HEK-293
additional information
knockdown of SIRT5 in induced onco-Dbl MEFs inhibits cell proliferation. Knockdown of SIRT5 also decreased the volume and number of colonies formed by the induced onco-Dbl MEFs in anchorage-independent growth assays. In breast cancer and lung cancer cell lines, SIRT5 knockdowns again inhibits proliferation and anchorage-independent growth. Expression of RNAi-resistant SIRT5 constructs rescue the proliferative defect caused by the SIRT5-targeted shRNAs
additional information
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knockdown of SIRT5 in induced onco-Dbl MEFs inhibits cell proliferation. Knockdown of SIRT5 also decreased the volume and number of colonies formed by the induced onco-Dbl MEFs in anchorage-independent growth assays. In breast cancer and lung cancer cell lines, SIRT5 knockdowns again inhibits proliferation and anchorage-independent growth. Expression of RNAi-resistant SIRT5 constructs rescue the proliferative defect caused by the SIRT5-targeted shRNAs
additional information
generation of SIRT5 knockout mice on the Sv129 background using the lentiviral SIRT5 shRNA plasmid sc-63027-SH
additional information
hepatic SIRT5-overexpressing ob/ob mouse model (ob/ob-SIRT5 OE) is established by CRISPR/Cas9 gene editing tool. Analysis of commercially available Sirt5 conditional knock-in C57BL/6 mice. Identification, quantification, and analysis of the malonylome and succinylome in response to hepatic overexpression of SIRT5 in ob/ob mice. Hepatic overexpression of SIRT5 in ob/ob mice demalonylates proteins in the glycolysis/gluconeogenesis pathway to improve glucose metabolism, and desuccinylates proteins in the oxidative phosphorylation pathway to facilitate fatty acid metabolism
additional information
-
hepatic SIRT5-overexpressing ob/ob mouse model (ob/ob-SIRT5 OE) is established by CRISPR/Cas9 gene editing tool. Analysis of commercially available Sirt5 conditional knock-in C57BL/6 mice. Identification, quantification, and analysis of the malonylome and succinylome in response to hepatic overexpression of SIRT5 in ob/ob mice. Hepatic overexpression of SIRT5 in ob/ob mice demalonylates proteins in the glycolysis/gluconeogenesis pathway to improve glucose metabolism, and desuccinylates proteins in the oxidative phosphorylation pathway to facilitate fatty acid metabolism
additional information
knockdown of SIRT5 expression in macrophages using siRNA
additional information
generation of SIRT5-KO mice. SIRT5-KO mice and wild-type controls undergo transverse aortic constriction (TAC) and are monitored for 16 weeks. In response to TAC, median survival is starkly decreased in SIRT5-KO mice compared with controls. No death is observed in the sham control groups for either genotype. SIRT5-KO mice have impaired systolic function 4 weeks post-TAC. These findings suggest that SIRT5-KO mice progress to cardiac dysfunction at an accelerated rate upon TAC-induced cardiac stress compared with controls, overview. SIRT5-KO mice demonstrate enhanced pathologic concentric hypertrophy in response to pressure overload, with key abnormalities in both cardiac relaxation and performance. Protein succinylation is increased in SIRT5KO hearts and abundant on enzymes in oxidative metabolism
additional information
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generation of SIRT5-KO mice. SIRT5-KO mice and wild-type controls undergo transverse aortic constriction (TAC) and are monitored for 16 weeks. In response to TAC, median survival is starkly decreased in SIRT5-KO mice compared with controls. No death is observed in the sham control groups for either genotype. SIRT5-KO mice have impaired systolic function 4 weeks post-TAC. These findings suggest that SIRT5-KO mice progress to cardiac dysfunction at an accelerated rate upon TAC-induced cardiac stress compared with controls, overview. SIRT5-KO mice demonstrate enhanced pathologic concentric hypertrophy in response to pressure overload, with key abnormalities in both cardiac relaxation and performance. Protein succinylation is increased in SIRT5KO hearts and abundant on enzymes in oxidative metabolism
additional information
generation of SIRT5 deletion mutant mice, homogenates prepared from whole SIRT5-/- liver show reduced Complex II-driven respiration. The enzymatic activities of Complex II and ATP synthase are also significantly reduced
additional information
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generation of SIRT5 deletion mutant mice, homogenates prepared from whole SIRT5-/- liver show reduced Complex II-driven respiration. The enzymatic activities of Complex II and ATP synthase are also significantly reduced
additional information
-
hepatic SIRT5-overexpressing ob/ob mouse model (ob/ob-SIRT5 OE) is established by CRISPR/Cas9 gene editing tool. Analysis of commercially available Sirt5 conditional knock-in C57BL/6 mice. Identification, quantification, and analysis of the malonylome and succinylome in response to hepatic overexpression of SIRT5 in ob/ob mice. Hepatic overexpression of SIRT5 in ob/ob mice demalonylates proteins in the glycolysis/gluconeogenesis pathway to improve glucose metabolism, and desuccinylates proteins in the oxidative phosphorylation pathway to facilitate fatty acid metabolism
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
a de novo protein synthesis inhibition experiment using cycloheximide shows that the SIRT5iso1-specific C-terminus is necessary for maintaining the stability of SIRT5iso1
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged enzyme from Escherichia coli strain Rosetta2(DE3) by nickel affinity chromatography and gel filtration
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
recombinant N-terminally His-tagged enzyme from Escherichia coli strain BL21(DE3) by cobalt affinity chromatography, tag cleavage by TEV protease, reverse cobalt affinity chromatography, and gel filtration
recombinant N-terminally His-tagged enzyme from Escherichia coli strain Transetta(DE3) by nickel affinity chromatography, tag cleavage by TEV protease, and ultrafiltration
recombinant N-terminally StrepII-tagged enzyme from Escherichia coli strain BL21(DE3) by affinity chromatography and gel filtration
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystals are grown by hanging drop vapor diffusion method, truncated SIRT5(34302) is cloned and expressed in Escherichia coli
expression as an N-terminal His-tagged protein in the Escherichia coli BL21(DE3)
gene SIRT5, alternative splicing of the human SIRT5 mRNA results in two distinct SIRT5 protein isoforms, differing at their C-termini, recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3, method, overview)
gene SIRT5, genotyping of the Ctl and OE mice. Sirt5 hepatic overexpressing (ob/ob-SIRT5 OE) mouse containing at least one allele of alternative Sirt5 gene and Alb-cre. The other one is control ob/ob mouse (ob/ob- control) containing only the floxed Sirt5 KI allele
gene SIRT5, recombinant expression of His-tagged enzyme in Escherichia coli strains Rosetta2(DE3) and BL21(DE3)
gene SIRT5, recombinant expression of N-terminally His-tagged enzyme in Escherichia coli strain BL21(DE3)
gene SIRT5, recombinant expression of N-terminally His-tagged enzyme in Escherichia coli strain Transetta(DE3)
gene SIRT5, recombinant expression of N-terminally StrepII-tagged enzyme in Escherichia coli strain BL21(DE3)
gene SIRT5, recombinant expression of tagged SIRT5 in HEK-293T cells, coexpression of wild-type and mutant protein kinase M2s, i.e. wild-type and mutants K62R/E, K135R/E, K311R/E, K498R/E, K311R/K498R, and K311E/K498E. Interactions between endogenous PKM2 and ectopically expressed FLAG-tagged PKM2, including the wild-type PKM2, the K311R mutant, and the succinylation-mimic K311E mutant, overview
gene SIRT5, transient overexpression of wild-type and mutant enzymes in HEK-293T cells or RAW-264.7 cells
the human SIRT5 gene encodes two main SIRT5 isoforms, SIRT5iso1 and SIRT5iso2 comprising 310 amino acids and 299 amino acids respectively, which differ slightly from one other at their C-termini, two other human SIRT5 isoforms (SIRT5iso3 and SIRT5iso4) have been reported. SIRT5iso3 is identical to SIRT5iso1 except that it lacks an internal sequence of 18 amino acids, while in SIRT5iso4 the initial 108 amino acids of SIRT5iso1 are missing, including the mitochondrial localization sequence
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
decreased expression of SIRT5 is found in cultured macrophages upon primary or second LPS stimulation
downregulated in the extranodal natural killer/T-cell lymphoma
enhanced expression of SIRT5 in the cerebral tissue of calorie restriction rats compared with rats that remained fed ad libitum
expression of SIRT5 increases during the progression of Alzheimers disease
in subcutaneous inguinal white adipose tissue, only Sirt5 expression is significantly increased after cold exposure
increased SIRT5 expression in human breast tumors is correlated with poor prognosis for patients
overexpression of AMP-activated protein kinase (AMPK) in mouse hepatocytes downregulates expression of SIRT5 mRNA by 58%. The antidiabetes drug metformin (1 mM), an established AMPK activator, reduces the mouse SIRT5 protein level by 44% in cultured hepatocytes and by 31% in liver in vivo (300 mg/kg, 7 d)
overexpression or metformin-mediated activation of AMPK inhibited SIRT5 expression
PGC-1alpha overexpression or food withdrawal increases SIRT5 mRNA and protein levels in mouse primary hepatocytes
SIRT5 expression is downregulated in human pancreatic ductal adenocarcinoma tissues. Activation of AMP-activated protein kinase (AMPK) causes SIRT5 downregulation
SIRT5 expression is reported to be regulated by two major cellular regulators of metabolism, peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha), and AMP-activated protein kinase (AMPK)
SIRT5 expression is reported to be regulated by two major cellular regulators of metabolism, peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha), and AMP-activated protein kinase (AMPK). PGC-1alpha overexpression or food withdrawal increases SIRT5 mRNA and protein levels in mouse primary hepatocytes, whereas overexpression or metformin-mediated activation of AMPK inhibits SIRT5 expression
SIRT5 expression is significantly decreased in human gastric cancer tissues
SIRT5 expression is significantly down-regulated in advanced prostate cancer
SIRT5 expression is upregulated in chordoma tissues and cells
SIRT5 is significantly down-regulated in cardiomyocytes upon oxidative stress
SIRT5 is upregulated during cellular transformation and supports proliferation and tumorigenesis
sirtuin 5 (SIRT5) is upregulated in patients with type 2 diabetes and in pancreatic beta cell lines
sirtuin 5 expression is upregulated with multiple rounds of bone marrow mesenchymal stem cells' passages
women with reduced ovarian reserve or advanced maternal age have decreased SIRT5 mRNA, protein and desuccinylation activity in granulosa and cumulus cells
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
drug development
medicine
pharmacology
desuccinylation mediated by SIRT5 is an indispensable and synergistic requirement for histidine combination therapy against 6-mercaptopurine resistance, which is undisclosed previously and demonstrates a rational strategy to ameliorate chemoresistance and protect pediatric patients with B-cell lineage acute lymphoblastic leukemia (B-ALL) from disease progression or relapse
diagnostics
elevated SIRT5 expression in human breast tumors correlates with poor patient prognosis
drug development
Sirt5 is a potential drug target for the treatment of cancer, Alzheimer's disease, and Parkinson's disease
medicine
SIRT5 may serve as a potential prognostic factor and drug target for intervention in non-small cell lung cancer. SIRT5 is overexpressed in human non-small cell lung cancer cells, high expression of SIRT5 predicts poor survival. SIRT5 knockdown makes lung cancer cells more sensitive to drug (cis-diamminedichloroplatinum, 5-fluorouracil or bleomycin) treatment in vitro and in vivo. Nrf2, which is a core transcription factor for lung cancer growth and drug resistance, is a target of SIRT5
medicine
pharmacological interventions on SIRT5 expression may be useful in the treatment of oxidative stress-related cardiac injury
medicine
SIRT5 is involved in influencing oocyte quality and in-vitro-fertilisation outcomes
medicine
study provides a valuable target to improve of osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) after many times of passages in vitro long-term passaged BM-MSCs exhibit upregulated SIRT5 expression, which leads to a decrease in UQCRC2 succinylation modification levels. This, in turn, enhances the activity of mitochondrial respiratory complex III and mitochondrial OXPHOS levels, impairs mitochondrial stability, and ultimately weakens the osteogenic differentiation capacity of BM-MSCs cells. Knockdown of SIRT5 can significantly reduce OXPHOS, maintain the normal function of mitochondria, and promote osteogenic differentiation of BM-MSCs even after many times of passages
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Starai, V.J.; Celic, I.; Cole, R.N.; Boeke, J.D.; Escalante-Semerena, J.C.
Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine
Science
298
2390-2392
2002
Salmonella enterica
brenda
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Homo sapiens (Q9NXA8), Homo sapiens
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EBioMedicine
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Homo sapiens (Q9NXA8), Homo sapiens, Mus musculus (A0A1Y7VM56), Mus musculus
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Homo sapiens (Q9NXA8), Homo sapiens, Danio rerio (Q6DHI5)
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Homo sapiens (Q9NXA8)
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SIRT5 stabilizes mitochondrial glutaminase and supports breast cancer tumorigenesis
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Homo sapiens (Q9NXA8), Homo sapiens
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BMC Cancer
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Histidine re-sensitizes pediatric acute lymphoblastic leukemia to 6-mercaptopurine through tetrahydrofolate consumption and SIRT5-mediated desuccinylation
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Dual modifying of MAVS at lysine 7 by SIRT3-catalyzed deacetylation and SIRT5-catalyzed desuccinylation orchestrates antiviral innate immunity
Proc. Natl. Acad. Sci. USA
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Tang, L.; Sun, Q.; Luo, J.; Peng, S.
Metformin hydrochloride improves hepatic glucolipid metabolism in diabetes progression through SIRT5-mediated ECHA desuccinylation
Sci. Rep.
15
7768
2025
Mus musculus (Q8K2C6), Homo sapiens (Q9NXA8)
brenda
Wang, T.; Tan, G.; Jiang, M.; Liu, G.; Li, W.; Qing, X.
SIRT5 inhibits glycolysis and nasal type extranodal NK/T cell lymphoma cell proliferation by catalyzing the desuccinylation of glucose-6-phosphate isomerase
Transl. Oncol.
51
102215
2025
Homo sapiens (Q9NXA8), Mus musculus (Q8K2C6)
brenda
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