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Information on EC 3.5.1.48 - acetylspermidine deacetylase
for references in articles please use BRENDA:EC3.5.1.48
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EC Tree 3 Hydrolases
3.5 Acting on carbon-nitrogen bonds, other than peptide bonds
3.5.1 In linear amides
3.5.1.48 acetylspermidine deacetylase
IUBMB Comments
It was initially thought that N1-acetylspermidine was the substrate for this deacetylase reaction but this has since been disproved by Marchant et al. .
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
- 3.5.1.48
- deacetylases
-
deacetylation
-
hdac11
- mycoplana
- ramosa
- pharmacology
- drug development
showSynonyms
hdac10, histone deacetylase 10, acetylpolyamine amidohydrolase, polyamine deacetylase, n8-acetylspermidine deacetylase, zhdac10, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
HDAC10
histone deacetylase 10
N1-acetylspermidine amidohydrolase
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-
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N8-acetyl-monoacetylspermidine deacetylase
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-
-
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N8-acetylspermidine deacetylase
polyamine deacetylase
N8-acetylspermidine deacetylase
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
N8-acetylspermidine + H2O = acetate + spermidine
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-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
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-
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SYSTEMATIC NAME
IUBMB Comments
N8-acetylspermidine amidohydrolase
It was initially thought that N1-acetylspermidine was the substrate for this deacetylase reaction [1] but this has since been disproved by Marchant et al. [3].
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CAS REGISTRY NUMBER
COMMENTARY
67339-07-5
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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
diacetylspermidine + H2O
acetate + spermidine
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Substrates: 81.9% activity of that of N8-acetylspermidine
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?
N-(3-aminopropyl)acetamide + H2O
propane-1,3-diamine + acetate
Substrates: very low activity
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?
N1,N8-diacetylspermidine + 2 H2O
2 acetate + spermidine
Substrates: moderate activity
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?
N1,N8-diacetylspermidine + H2O
2 acetate + spermidine
Substrates: high activity
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?
N1,N8-diacetylspermidine + H2O
acetate + spermidine
Substrates: -
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?
Nalpha,Nepsilon-diacetyl-L-lysinamide + H2O
?
Substrates: low activity
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?
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin + H2O
?
Substrates: very low activity
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?
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin + H2O
?
Substrates: low activity
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?
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin + H2O
?
Substrates: very low activity
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?
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin + H2O
?
Substrates: low activity
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?
acetylcadaverine + H2O
acetate + cadaverine
Substrates: high acitivity
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?
acetylcadaverine + H2O
acetate + cadaverine
Substrates: high acitivity
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?
acetylputrescine + H2O
acetate + putrescine
Substrates: high acitivity
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?
acetylputrescine + H2O
acetate + putrescine
Substrates: high acitivity
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?
N-(8-aminooctyl)acetamide + H2O
octane-1,8-diamine + acetate
Substrates: moderate to high activity
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?
N-(8-aminooctyl)acetamide + H2O
octane-1,8-diamine + acetate
Substrates: moderate activity
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?
N-butylacetamide + H2O
butan-1-amine + acetate
Substrates: very low activity
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?
N-butylacetamide + H2O
butan-1-amine + acetate
Substrates: low activity
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?
N1-acetylspermidine + H2O
acetate + spermidine
Substrates: very low activity
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?
N1-acetylspermidine + H2O
acetate + spermidine
Substrates: low activity
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?
N1-acetylspermidine + H2O
acetate + spermidine
-
Substrates: low activity
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?
N1-acetylspermidine + H2O
acetate + spermidine
-
Substrates: -
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?
N1-acetylspermidine + H2O
acetate + spermidine
-
Substrates: -
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?
N1-acetylspermine + H2O
acetate + spermine
Substrates: very low activity
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?
N1-acetylspermine + H2O
acetate + spermine
Substrates: low activity
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?
N8-acetylspermidine + H2O
acetate + spermidine
Substrates: -
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?
N8-acetylspermidine + H2O
acetate + spermidine
Substrates: best substrate
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?
N8-acetylspermidine + H2O
acetate + spermidine
Substrates: -
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?
N8-acetylspermidine + H2O
acetate + spermidine
Substrates: the enzyme shows high substrate specificity for N8-acetylspermidine
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?
N8-acetylspermidine + H2O
acetate + spermidine
Substrates: -
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?
N8-acetylspermidine + H2O
acetate + spermidine
Substrates: highly preferred substrate, used as aminopropionyl aminocumarin derivative, Ac-spermidine-AMC
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?
N8-acetylspermidine + H2O
acetate + spermidine
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Substrates: highest activity
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?
N8-acetylspermidine + H2O
acetate + spermidine
Substrates: -
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?
N8-acetylspermidine + H2O
acetate + spermidine
Substrates: best substrate
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?
N8-acetylspermidine + H2O
acetate + spermidine
-
Substrates: -
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?
N8-acetylspermidine + H2O
acetate + spermidine
-
Substrates: -
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?
N8-acetylspermidine + H2O
acetate + spermidine
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Substrates: preferred substrate
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?
N8-acetylspermidine + H2O
acetate + spermidine
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Substrates: involvement in cell growth and differentiation
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?
N8-acetylspermidine + H2O
acetate + spermidine
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Substrates: involvement in controlling the levels of polyamines and acetylated polyamines in tissues
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?
Nalpha-acetyl-L-alanyl-Nepsilon-acetyl-L-lysyl-L-alaninamide + H2O
?
Substrates: low activity
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?
Nalpha-acetyl-L-alanyl-Nepsilon-acetyl-L-lysyl-L-alaninamide + H2O
?
Substrates: low activity
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?
additional information
?
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Substrates: zebrafish HDAC10 complexed with a transition-state analogue inhibitor reveals that a glutamate gatekeeper and a sterically constricted active site confer specificity for N8-acetylspermidine hydrolysis and disfavour acetyllysine hydrolysis. The N4 amino group of N8-acetylspermidine is recognized by a direct hydrogen bond with E117. No activity with TK(ac)PIW, AK(ac)P, GAK(ac), AK(ac), AK(ac)A, K(ac)NL, K(ac)NL, and GAK(ac)NLQ
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?
additional information
?
-
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Substrates: zebrafish HDAC10 complexed with a transition-state analogue inhibitor reveals that a glutamate gatekeeper and a sterically constricted active site confer specificity for N8-acetylspermidine hydrolysis and disfavour acetyllysine hydrolysis. The N4 amino group of N8-acetylspermidine is recognized by a direct hydrogen bond with E117. No activity with TK(ac)PIW, AK(ac)P, GAK(ac), AK(ac), AK(ac)A, K(ac)NL, K(ac)NL, and GAK(ac)NLQ
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?
additional information
?
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Substrates: histone deacetylase 10 (HDAC10) from Danio rerio is a highly specific N8-acetylspermidine deacetylase. No activity with N1-acetylspermidine and N1-acetylspermine
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?
additional information
?
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Substrates: histone deacetylase 10 (HDAC10) from Danio rerio is a highly specific N8-acetylspermidine deacetylase. No activity with N1-acetylspermidine and N1-acetylspermine
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?
additional information
?
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Substrates: the molecular gatekeeper residue E274 (zebrafish HDAC10 numbering) establishes electrostatic complementarity for cationic polyamine substrates. A 310 helix with consensus sequence P23(E,A)CE26 (the PEACE motif) sterically constricts the active site so as to favor the binding of long, slender polyamines
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additional information
?
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Substrates: enzyme zHDAC10 shows a narrow substrate specificity
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additional information
?
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Substrates: development and evaluation of a fluorescent acetylspermidine deacetylation assay for HDAC10 using an aminocoumarin-labelled acetyl-spermidine derivative to measure its PDAC activity, which is suitable for high-throughput screening, synthesis of a protected aminopropionyl aminocumarin, mechanism, overview. HDAC10 has strong preferences for deacetylation of oligoamine substrates like acetyl-putrescine or -spermidine. Hence, it is also termed a polyamine deacetylase (PDAC). The preferential binding of N8-acetylspermidine versus N1-acetylspermidine is explained by the position and orientation of the secondary amino group. A distance of four carbons between the amide moiety and the secondary amino group is favorable for the substrate recognition
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additional information
?
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Substrates: the conserved glutamate gatekeeper and a sterically constricted active site confer specificity for N8-acetylspermidine hydrolysis and disfavour acetyllysine hydrolysis. Analysis of the intermolecular interactions of N8-acetylspermidine in the active site of hHDAC10 based on the structure of the Danio rerio enzyme-inhibitor crystal structure zHDAC10-AAT complex. No activity with N-(3-aminopropyl)acetamide, TK(ac)PIW, AK(ac)P, GAK(ac), AK(ac), K(ac)NL, K(ac)NL, and GAK(ac)NLQ
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?
additional information
?
-
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Substrates: the conserved glutamate gatekeeper and a sterically constricted active site confer specificity for N8-acetylspermidine hydrolysis and disfavour acetyllysine hydrolysis. Analysis of the intermolecular interactions of N8-acetylspermidine in the active site of hHDAC10 based on the structure of the Danio rerio enzyme-inhibitor crystal structure zHDAC10-AAT complex. No activity with N-(3-aminopropyl)acetamide, TK(ac)PIW, AK(ac)P, GAK(ac), AK(ac), K(ac)NL, K(ac)NL, and GAK(ac)NLQ
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?
additional information
?
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Substrates: histone deacetylase 10 (HDAC10) from Homo sapiens is a highly specific N8-acetylspermidine deacetylase. No activity with N1-acetylspermidine and N1-acetylspermine
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?
additional information
?
-
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Substrates: histone deacetylase 10 (HDAC10) from Homo sapiens is a highly specific N8-acetylspermidine deacetylase. No activity with N1-acetylspermidine and N1-acetylspermine
Products: -
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?
additional information
?
-
-
Substrates: the bacterial enzyme from Mycoplana ramosa has broader substrate specificity in comparison with mammalian enzyme. Its substrates include both small and large acetylpolyamines such as acetylputrescine, acetylcadaverine, N1- and N8-acetylspermidine, and N1-acetylspermine
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?
additional information
?
-
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Substrates: usage of the commercially available Fluor-de-Lys deacetylase fluorogenic substrate fir enzyme activity assays
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?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
N1-acetylspermidine + H2O
acetate + spermidine
-
Substrates: -
Products: -
Products: -
?
additional information
?
-
-
Substrates: the bacterial enzyme from Mycoplana ramosa has broader substrate specificity in comparison with mammalian enzyme. Its substrates include both small and large acetylpolyamines such as acetylputrescine, acetylcadaverine, N1- and N8-acetylspermidine, and N1-acetylspermine
Products: -
Products: -
?
N8-acetylspermidine + H2O
acetate + spermidine
Substrates: -
Products: -
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?
N8-acetylspermidine + H2O
acetate + spermidine
Substrates: -
Products: -
Products: -
?
N8-acetylspermidine + H2O
acetate + spermidine
Substrates: the enzyme shows high substrate specificity for N8-acetylspermidine
Products: -
Products: -
?
N8-acetylspermidine + H2O
acetate + spermidine
Substrates: -
Products: -
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?
N8-acetylspermidine + H2O
acetate + spermidine
Substrates: -
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?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Zn2+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(1-[[4-(hydroxycarbamoyl)phenyl]methyl]-1H-indol-3-yl)-N,N-dimethylmethanaminium
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(2E)-3-(2,4-dichlorophenyl)-N-hydroxyprop-2-enamide
over 95% inhibition at 0.001 mM
(2E)-3-(2-bromo-5-fluorophenyl)-N-hydroxyprop-2-enamide
50% inhibition at 0.001 mM
(2E)-3-(2-bromo-5-methoxyphenyl)-N-hydroxyprop-2-enamide
39% inhibition at 0.001 mM
(2E)-3-(2-chlorophenyl)-N-hydroxyprop-2-enamide
73% inhibition at 0.001 mM
(2E)-3-(3-chlorophenyl)-N-hydroxyprop-2-enamide
69% inhibition at 0.001 mM
(2E)-3-(dibenzo[b,d]thiophen-3-yl)-N-hydroxyprop-2-enamide
54% inhibition at 0.001 mM
(2E)-3-[4-(benzyloxy)-3-methoxyphenyl]-N-hydroxyprop-2-enamid
30% inhibition at 0.001 mM
-
(2E)-N-hydroxy-3-(naphthalen-2-yl)prop-2-enamide
64% inhibition at 0.001 mM. Docking into the active site of drHDAC10 shows that the compound is able to coordinate the zinc ion in a bidentate manner and undergoes the three common hydrogen bond interactions with the conserved histidine and tyrosine residues at the bottom of the tunnel. The naphthyl capping group is embedded in the lysine tunnel where it undergoes Pi-Pi stacking interactions with Trp205 and Phe146
(2E)-N-hydroxy-3-[2-[(3-methoxyphenyl)methoxy]phenyl]prop-2-enamide
24% inhibition at 0.001 mM
1-[2-(benzylamino)ethyl]-N-hydroxypiperidine-4-carboxamide
docking study, analysis of the crystal structure of HDAC10-1-[2-(benzylamino)ethyl]-N-hydroxypiperidine-4-carboxamide complex at 2.18 A resolution
2-(1-[[4-(hydroxycarbamoyl)phenyl]methyl]-1H-indol-3-yl)-N,N-dimethylethan-1-aminium
-
2-(4-bromophenyl)-N-hydroxy-1,3-oxazole-4-carboxamide
over 95% inhibition at 0.001 mM
3-(4-chlorobenzamido)-N-hydroxy-4-methoxybenzamide
31% inhibition at 0.001 mM
3-(benzyloxy)-N-hydroxy-4-methoxybenzamide
below 10% inhibition at 0.001 mM
3-[(3-aminopropyl)amino]-N-hydroxyhexanamide
-
non-competitive inhibition, Ki: 1 nM
3-[3-(benzyloxy)benzamido]-4-chloro-N-hydroxybenzamide
20% inhibition at 0.001 mM
4-(dimethylamino)-N-[[4-(hydroxycarbamoyl)cyclohexyl]methyl]benzamide
42% inhibition at 0.001 mM
4-(dimethylamino)-N-[[4-(hydroxycarbamoyl)phenyl]methyl]benzamide
19% inhibition at 0.001 mM
4-chloro-N-hydroxy-1-benzothiophene-2-carboxamide
56% inhibition at 0.001 mM
abexinostat
in clinical trials, over 95% inhibition at 0.001 mM, a HDAC pan-inhibitor
echothiopate
-
non-competitive inhibition, Ki: 0.4 mM, i.e.ammonium, (2-mercaptoethyl)trimethyl-, S-ester with O,O-diethyl phosphorothioate
methyl N-[8-(hydroxyamino)-8-oxooctanoyl]-3-(6-methylpyridin-2-yl)-L-alaninate
64% inhibition at 0.001 mM
methyl N-[8-(hydroxyamino)-8-oxooctanoyl]-3-(6-methylpyridin-2-yl)alaninate
51% inhibition at 0.001 mM
N',N''-bis(tert-butoxycarbonyl)-6-[(3-aminopropyl)amino]-N-hydroxyhexanamide
-
-
N',N''-bis(tert-butoxycarbonyl)-6-[(3-aminopropyl)amino]-N-methoxy-N-methylhexanamide
-
-
N,N'-bis(tert-butoxycarbonyl)-7-[(3-aminopropyl)amino]-1,1,1-trifluoroheptan-2-ol
-
-
N,N'-bis(tert-butoxycarbonyl)-7-[(3-aminopropyl)amino]-1,1,1-trifluoroheptan-2-one
-
-
N,N'-bis(tert-butoxycarbonyl)-7-[(3-aminopropyl)amino]-1-bromoheptan-2-ol
-
-
N,N'-bis(tert-butoxycarbonyl)-7-[(3-aminopropyl)amino]-1-bromoheptan-2-one
-
-
N,N'-bis(tert-butoxycarbonyl)-7-[(3-aminopropyl)amino]-1-methoxyheptan-2-ol
-
-
N,N'-bis(tert-butoxycarbonyl)-7-[(3-aminopropyl)amino]-1-methoxyheptan-2-one
-
-
N-hydroxy-1-[(4-methoxyphenyl)methyl]-1H-indole-6-carboxamide
14-17% inhibition at 0.0001-0.001 mM
N-hydroxy-2-(naphthalen-2-yl)-1,3-oxazole-4-carboxamide
34% inhibition at 0.001 mM
N-hydroxy-2-(thiophen-2-yl)-1,3-oxazole-4-carboxamide
37% inhibition at 0.001 mM
N-hydroxy-4-methoxy-3-[(2-phenylethyl)amino]benzamide
19% inhibition at 0.001 mM
N-[5-(hydroxycarbamoyl)-2-methoxyphenyl][1,1'-biphenyl]-3-carboxamide
below 10% inhibition at 0.001 mM
N-[5-(hydroxycarbamoyl)-2-methoxyphenyl][1,1'-biphenyl]-4-carboxamide
below 10% inhibition at 0.001 mM
N1,N3-bis(tert-butoxycarbonyl)-N1-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pentyl]propane-1,3-diamine
-
-
N1,N3-bis(tert-butoxycarbonyl)-N1-[5-(methylsulfonyl)pentyl]propane-1,3-diamine
-
-
N1,N3-bis(tert-butoxycarbonyl)-N1-[5-(methylthio)pentyl]propane-1,3-diamine
-
-
N1,N3-bis(tert-butoxycarbonyl)-N1-[5-(oxiran-2-yl)pentyl]propane-1,3-diamine
-
-
N8-Acetylspermidine
-
stimulation of cell growth due to inhibition of N8-acetylspremidine deacetylase, maximum cell growth stimulation above 1 mM
panobinostat
for cancer treatment, over 95% inhibition at 0.001 mM, a HDAC pan-inhibitor
quisinostat
in clinical trials, 91% inhibition at 0.001 mM, a HDAC pan-inhibitor
S-{N,N'-bis(tert-butoxycarbonyl)-5-[(3-aminopropyl)amino]pentyl} thioacetate
-
-
S-{N,N'-bis(tert-butoxycarbonyl)-7-[(3-aminopropyl)amino]-2-oxoheptyl}thioacetate
-
-
tert-butyl [(1-[[4-(hydroxycarbamoyl)phenyl]methyl]-1H-indol-3-yl)methyl]carbamate
-
vorinostat
for treatment of cutaneous T-cell lymphoma, 43% inhibition at 0.001 mM
7-[(3-aminopropyl)amino]-1,1,1-trifluoroheptan-2-one
AAT, binds as a tetrahedral gem-diolate to both APAH (acetylpolyamine amidohydrolase, EC 3.5.1.62) and HDAC10, thereby mimicking the tetrahedral intermediate and its flanking transition states in catalysis
7-[(3-aminopropyl)amino]-1,1,1-trifluoroheptan-2-one
AAT, enzyme-bound structure analysis, overview. This inhibitor binds as a transition state analogue
7-[(3-aminopropyl)amino]-1,1,1-trifluoroheptan-2-one
AAT, binds as a tetrahedral gem-diolate to both APAH (acetylpolyamine amidohydrolase, EC 3.5.1.62) and HDAC10, thereby mimicking the tetrahedral intermediate and its flanking transition states in catalysis
7-[(3-aminopropyl)amino]-1,1,1-trifluoroheptan-2-one
AAT, the inhibitor binds as a transition state analogue
7-[N-(3-aminopropyl)amino]heptan-2-one
-
stimulation of cell growth due to inhibition of N8-acetylspermidine deacetylase, maximum cell growth stimulation at 0.1 mM
7-[N-(3-aminopropyl)amino]heptan-2-one
-
induction of neurite outgrowth at 0.001 to 0.0001 mM due to inhibition of N8-acetylspermidine deacetylase, involvement in differentiation of PC 12 cells
tubastatin A
tubastatin A has been designed to selectively inhibit HDAC6, the other class IIb isozyme, but is more selective for the inhibition of HDAC10 by nearly 8fold. Functional importance of the tertiary amino group of tubastatin A by compared to its oxa analogue. The active site of A24E-D94A zebrafish HDAC10 thus mimics the active site of human HDAC10
tubastatin A
over 95% inhibition at 0.001 mM. Predicted binding modes of tubastatin A with different HDAC isoforms, overview
additional information
isozyme-selective inhibition, structure-function relationship of inhibitors. Analysis of the X-ray crystal structures of the HDAC10 variant complexed with tubastatin A, oxa-tubastatin A, and indole analogues (1-[[4-(hydroxycarbamoyl)phenyl]methyl]-1H-indol-3-yl)-N,N-dimethylmethanaminium, 2-(1-[[4-(hydroxycarbamoyl)phenyl]methyl]-1H-indol-3-yl)-N,N-dimethylethan-1-aminium, N-hydroxy-4-[[3-(2-hydroxyethyl)-1H-indol-1-yl]methyl]benzamide, and N-hydroxy-4-[(1H-indol-1-yl)methyl]benzamide, bearing pendant tertiary amines, detailed overview. Inhibitors capable of hydrogen bonding with gatekeeper E274 exhibit high affinity and selectivity for HDAC10 over HDAC6 (the other class IIb isozyme), overview. Slender polyamine-like inhibitor structures are not exclusively required for selective, high affinity binding to HDAC10
-
additional information
identification of potent inhibitors of HDAC10-mediated spermidine deacetylation in vitro, design of inhibitors with a basic moiety in appropriate distance to the zinc binding hydroxamate that show potent inhibition of HDAC10 with high selectivity and selective cellular target engagement for HDAC10, docking study, overview
-
additional information
-
design, synthesis, and evaluation of N8-acetylspermidine analogues bearing different zinc binding groups as potential inhibitors of the enzyme, overview. Most of the synthesized compounds exhibit modest potency, with IC50 values in the mid-micromolar range, but compounds bearing hydroxamate or trifluoromethylketone zinc binding groups exhibit enhanced inhibitory potency in the mid-nanomolar range. Three compounds exhibit very poor inhibitory potency against th enzyme, 6-[(3-aminopropyl)amino]hexanoic acid, S-{5-[(3-aminopropyl)amino]pentyl} thioacetate, and N1-[5-(methylsulfonyl)pentyl]propane-1,3-diamine dihydrochloride
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Adenocarcinoma of Lung
HDAC10 Regulates Cancer Stem-Like Cell Properties in KRAS-Driven Lung Adenocarcinoma.
Adrenal Cortex Neoplasms
Comprehensive DNA methylation analysis of benign and malignant adrenocortical tumors.
Carcinogenesis
HDAC10 expression is associated with DNA mismatch repair gene and is a predictor of good prognosis in colon carcinoma.
Carcinogenesis
HDAC10 Regulates Cancer Stem-Like Cell Properties in KRAS-Driven Lung Adenocarcinoma.
Carcinogenesis
Histone deacetylase 10 exerts anti-tumor effects on cervical cancer via a novel microRNA-223/TXNIP/Wnt/?-catenin pathway.
Carcinogenesis
Histone deacetylase 10 exerts antitumor effects on cervical cancer via a novel microRNA-223/TXNIP/Wnt/?-catenin pathway.
Carcinoma
HDAC10 expression is associated with DNA mismatch repair gene and is a predictor of good prognosis in colon carcinoma.
Carcinoma
HDAC10 Is Positively Associated With PD-L1 Expression and Poor Prognosis in Patients With NSCLC.
Carcinoma
Histone Deacetylase (HDAC) 10 Suppresses Cervical Cancer Metastasis through Inhibition of Matrix Metalloproteinase (MMP) 2 and 9 Expression.
Carcinoma
Histone deacetylase 10 suppresses proliferation and invasion by inhibiting the phosphorylation of ?-catenin and serves as an independent prognostic factor for human clear cell renal cell carcinoma.
Carcinoma, Hepatocellular
Growth attenuation is associated with histone deacetylase 10-induced autophagy in the liver.
Carcinoma, Renal Cell
Histone deacetylase 10 suppresses proliferation and invasion by inhibiting the phosphorylation of ?-catenin and serves as an independent prognostic factor for human clear cell renal cell carcinoma.
Carcinoma, Squamous Cell
Histone Deacetylase (HDAC) 10 Suppresses Cervical Cancer Metastasis through Inhibition of Matrix Metalloproteinase (MMP) 2 and 9 Expression.
Colonic Neoplasms
HDAC10 expression is associated with DNA mismatch repair gene and is a predictor of good prognosis in colon carcinoma.
Kidney Neoplasms
DDX39B Predicts Poor Survival and Associated with Clinical Benefit of Anti-PD-L1 Therapy in ccRCC.
Leukemia, Lymphocytic, Chronic, B-Cell
Expression and Function of Histone Deacetylase 10 (HDAC10) in B Cell Malignancies.
Lung Neoplasms
4-hydroxyphenylpyruvate dioxygenase promotes lung cancer growth via pentose phosphate pathway (PPP) flux mediated by LKB1-AMPK/HDAC10/G6PD axis.
Lung Neoplasms
HDAC10 Is Positively Associated With PD-L1 Expression and Poor Prognosis in Patients With NSCLC.
Lung Neoplasms
HDAC10 Regulates Cancer Stem-Like Cell Properties in KRAS-Driven Lung Adenocarcinoma.
Lymphatic Metastasis
Histone Deacetylase (HDAC) 10 Suppresses Cervical Cancer Metastasis through Inhibition of Matrix Metalloproteinase (MMP) 2 and 9 Expression.
Lymphoma
Expression and Function of Histone Deacetylase 10 (HDAC10) in B Cell Malignancies.
Lymphoma, Mantle-Cell
Expression and Function of Histone Deacetylase 10 (HDAC10) in B Cell Malignancies.
Malnutrition
Growth attenuation is associated with histone deacetylase 10-induced autophagy in the liver.
Neoplasm Metastasis
Histone Deacetylase (HDAC) 10 Suppresses Cervical Cancer Metastasis through Inhibition of Matrix Metalloproteinase (MMP) 2 and 9 Expression.
Neoplasm Metastasis
Histone deacetylase 10 exerts anti-tumor effects on cervical cancer via a novel microRNA-223/TXNIP/Wnt/?-catenin pathway.
Neoplasm Metastasis
Histone deacetylase 10 exerts antitumor effects on cervical cancer via a novel microRNA-223/TXNIP/Wnt/?-catenin pathway.
Neoplasm Metastasis
Histone deacetylase 10 suppresses proliferation and invasion by inhibiting the phosphorylation of ?-catenin and serves as an independent prognostic factor for human clear cell renal cell carcinoma.
Neoplasm Metastasis
Suppression of lung cancer cell invasion and metastasis by connexin43 involves the secretion of follistatin-like 1 mediated via histone acetylation.
Neoplasms
4-hydroxyphenylpyruvate dioxygenase promotes lung cancer growth via pentose phosphate pathway (PPP) flux mediated by LKB1-AMPK/HDAC10/G6PD axis.
Neoplasms
Binding of N8-Acetylspermidine Analogues to Histone Deacetylase 10 Reveals Molecular Strategies for Blocking Polyamine Deacetylation.
Neoplasms
Decreased expression of histone deacetylase 10 predicts poor prognosis of gastric cancer patients.
Neoplasms
Expression and Function of Histone Deacetylase 10 (HDAC10) in B Cell Malignancies.
Neoplasms
HDAC10 expression is associated with DNA mismatch repair gene and is a predictor of good prognosis in colon carcinoma.
Neoplasms
HDAC10 Regulates Cancer Stem-Like Cell Properties in KRAS-Driven Lung Adenocarcinoma.
Neoplasms
Histone Deacetylase (HDAC) 10 Suppresses Cervical Cancer Metastasis through Inhibition of Matrix Metalloproteinase (MMP) 2 and 9 Expression.
Neoplasms
Histone deacetylase 10 exerts anti-tumor effects on cervical cancer via a novel microRNA-223/TXNIP/Wnt/?-catenin pathway.
Neoplasms
Histone deacetylase 10 exerts antitumor effects on cervical cancer via a novel microRNA-223/TXNIP/Wnt/?-catenin pathway.
Neoplasms
Histone deacetylase 10 suppresses proliferation and invasion by inhibiting the phosphorylation of ?-catenin and serves as an independent prognostic factor for human clear cell renal cell carcinoma.
Neoplasms
Histone deacetylase 10-promoted autophagy as a druggable point of interference to improve the treatment response of advanced neuroblastomas.
Neoplasms
The HDAC6/8/10 inhibitor TH34 induces DNA damage-mediated cell death in human high-grade neuroblastoma cell lines.
Neoplasms
X-ray Crystallographic Snapshots of Substrate Binding in the Active Site of Histone Deacetylase 10.
Neuroblastoma
Binding of N8-Acetylspermidine Analogues to Histone Deacetylase 10 Reveals Molecular Strategies for Blocking Polyamine Deacetylation.
Neuroblastoma
Dual role of HDAC10 in lysosomal exocytosis and DNA repair promotes neuroblastoma chemoresistance.
Neuroblastoma
Histone deacetylase 10-promoted autophagy as a druggable point of interference to improve the treatment response of advanced neuroblastomas.
Neuroblastoma
Selective Inhibition of Histone Deacetylase 10: Hydrogen Bonding to the Gatekeeper Residue is Implicated.
Neuroblastoma
The HDAC6/8/10 inhibitor TH34 induces DNA damage-mediated cell death in human high-grade neuroblastoma cell lines.
Pulmonary Disease, Chronic Obstructive
Gene expression profile of human lung in a relatively early stage of COPD with emphysema.
Stomach Neoplasms
Decreased expression of histone deacetylase 10 predicts poor prognosis of gastric cancer patients.
Stomach Neoplasms
Inhibition of histone deacetylase 10 induces thioredoxin-interacting protein and causes accumulation of reactive oxygen species in SNU-620 human gastric cancer cells.
Uterine Cervical Neoplasms
Histone Deacetylase (HDAC) 10 Suppresses Cervical Cancer Metastasis through Inhibition of Matrix Metalloproteinase (MMP) 2 and 9 Expression.
Uterine Cervical Neoplasms
Histone deacetylase 10 exerts anti-tumor effects on cervical cancer via a novel microRNA-223/TXNIP/Wnt/?-catenin pathway.
Uterine Cervical Neoplasms
Histone deacetylase 10 exerts antitumor effects on cervical cancer via a novel microRNA-223/TXNIP/Wnt/?-catenin pathway.
Uterine Cervical Neoplasms
Oncogenic miRNA-1908 targets HDAC10 and promotes the aggressive phenotype of cervical cancer cell.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.01 - 0.07
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
0.066 - 0.15
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
0.14
Nalpha,Nepsilon-diacetyl-L-lysinamide
pH 8.0, 22°C, recombinant enzyme
0.01
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant enzyme
0.017
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant D94A
0.022
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant wild-type enzyme
0.06
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant N93A
0.06
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant deletion mutant DELTAnuA2
0.07
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant E274L
0.066
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant wild-type enzyme
0.07
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant E274L
0.11
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant enzyme
0.11
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant N93A
0.15
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant D94A
0.27
N8-Acetylspermidine
pH 8.0, 22°C, recombinant deletion mutant DELTAnuA2
0.06
Nalpha-acetyl-L-alanyl-Nepsilon-acetyl-L-lysyl-L-alaninamide
pH 8.0, 22°C, recombinant enzyme
0.08
Nalpha-acetyl-L-alanyl-Nepsilon-acetyl-L-lysyl-L-alaninamide
pH 8.0, 22°C, recombinant wild-type enzyme
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00007 - 0.053
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
0.0013 - 0.21
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
0.0092
Nalpha,Nepsilon-diacetyl-L-lysinamide
pH 8.0, 22°C, recombinant enzyme
0.00007
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant N93A
0.00033
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant wild-type enzyme
0.00038
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant enzyme
0.00046
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant D94A
0.021
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant deletion mutant DELTAnuA2
0.053
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant E274L
0.0013
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant N93A
0.0013
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant D94A
0.0015
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant wild-type enzyme
0.008
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant enzyme
0.21
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant E274L
0.082
N8-Acetylspermidine
pH 8.0, 22°C, recombinant deletion mutant DELTAnuA2
0.0006
Nalpha-acetyl-L-alanyl-Nepsilon-acetyl-L-lysyl-L-alaninamide
pH 8.0, 22°C, recombinant enzyme
0.013
Nalpha-acetyl-L-alanyl-Nepsilon-acetyl-L-lysyl-L-alaninamide
pH 8.0, 22°C, recombinant wild-type enzyme
additional information
additional information
steady-state kinetics of wild-type and mutant enzymes
-
additional information
additional information
-
steady-state kinetics of wild-type and mutant enzymes
-
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0012 - 0.757
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
0.0087 - 8.84
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
0.066
Nalpha,Nepsilon-diacetyl-L-lysinamide
pH 8.0, 22°C, recombinant enzyme
0.0012
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant N93A
0.015
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant wild-type enzyme
0.027
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant D94A
0.038
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant enzyme
0.35
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant deletion mutant DELTAnuA2
0.757
7-(Nalpha-acetyl-glycyl-L-alanyl-Nepsilon-acetyl-L-lysyl)amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant E274L
0.0087
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant D94A
0.012
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant N93A
0.023
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant wild-type enzyme
0.072
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant enzyme
8.84
7-(Nalpha-acetyl-L-arginyl-glycyl-Nepsilon-acetyl-L-lysyl)-amino-4-methylcoumarin
pH 8.0, 22°C, recombinant mutant E274L
0.304
N8-Acetylspermidine
pH 8.0, 22°C, recombinant deletion mutant DELTAnuA2
0.01
Nalpha-acetyl-L-alanyl-Nepsilon-acetyl-L-lysyl-L-alaninamide
pH 8.0, 22°C, recombinant enzyme
0.163
Nalpha-acetyl-L-alanyl-Nepsilon-acetyl-L-lysyl-L-alaninamide
pH 8.0, 22°C, recombinant wild-type enzyme
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000001
3-[(3-aminopropyl)amino]-N-hydroxyhexanamide
-
non-competitive inhibition
0.4
echothiopate
-
non-competitive inhibition, i.e.ammonium, (2-mercaptoethyl)trimethyl-, S-ester with O,O-diethyl phosphorothioate
0.0007
7-[(3-aminopropyl)amino]-1,1,1-trifluoroheptan-2-one
pH 8.0, 22°C, recombinant enzyme
0.0007
7-[(3-aminopropyl)amino]-1,1,1-trifluoroheptan-2-one
pH 8.0, 22°C, recombinant wild-type enzyme
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000005
(1-[[4-(hydroxycarbamoyl)phenyl]methyl]-1H-indol-3-yl)-N,N-dimethylmethanaminium
Danio rerio
pH and temperature not specified in the publication
0.000037
1-(2-((4-bromobenzyl)amino)ethyl)-N-hydroxypiperidine-4-carboxamide
Danio rerio
pH 7.9, 25°C
0.000064
1-[2-(benzylamino)ethyl]-N-hydroxypiperidine-4-carboxamide
Danio rerio
pH 7.9, 25°C
0.00002
2-(1-[[4-(hydroxycarbamoyl)phenyl]methyl]-1H-indol-3-yl)-N,N-dimethylethan-1-aminium
Danio rerio
pH and temperature not specified in the publication
0.000063
N-hydroxy-4-[(1H-indol-1-yl)methyl]benzamide
Danio rerio
pH and temperature not specified in the publication
0.000079
N-hydroxy-4-[[3-(2-hydroxyethyl)-1H-indol-1-yl]methyl]benzamide
Danio rerio
pH and temperature not specified in the publication
0.00063
oxa-tubastatin A
Danio rerio
pH and temperature not specified in the publication
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
25
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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
evolution
malfunction
metabolism
since the polyamine spermidine is also implicated as an inducer of autophagy, HDAC10 may represent a link between polyamine metabolism and autophagic cellular survival mechanisms
physiological function
additional information
evolution
the enzyme adopts the characteristic arginase-deacetylase fold and employ a Zn2+-activated water molecule for catalysis. The active sites of HDAC10 and APAH (acetylpolyamine amidohydrolase, EC 3.5.1.62) are sterically constricted to enforce specificity for long, slender polyamine substrates and exclude bulky peptides and proteins containing acetyl-L-lysine. The tertiary structure (a unique 310 helix defined by the P(E,A)CE motif) provides the steric constriction that directs the polyamine substrate specificity of HDAC10. Structure and catalytic mechanism of polyamine deacetylases, comparison of HDAC and APAH, overview
evolution
the enzyme adopts the characteristic arginase-deacetylase fold and employ a Zn2+-activated water molecule for catalysis. The active sites of HDAC10 and APAH (acetylpolyamine amidohydrolase, EC 3.5.1.62) are sterically constricted to enforce specificity for long, slender polyamine substrates and exclude bulky peptides and proteins containing acetyl-L-lysine. The tertiary structure (a unique 310 helix defined by the P(E,A)CE motif) provides the steric constriction that directs the polyamine substrate specificity of HDAC10. Structure and catalytic mechanism of polyamine deacetylases, comparison of HDAC and APAH, overview
evolution
bacterial polyamine deacetylase, Zn2+-dependent acetylpolyamine amidohydrolase, from the deep earth halophile Marinobacter subterrani (msAPAH) shares 53% amino acid sequence identity with the acetylpolyamine amidohydrolase from Mycoplana ramosa (mrAPAH) and 22% amino acid sequence identity with the catalytic domain of histone deacetylase 10 from Danio rerio (zebrafish, zHDAC10), the eukaryotic polyamine deacetylase. Structural comparisons indicate that the arginases and deacetylases divergently evolved from a common ancestral alpha/beta-metallohydrolase despite sharing low amino acid sequence identities generally ranging 10-15%
malfunction
deletion of the PEACE motif diminishes N8-acetylspermidine deacetylase activity 15fold and increases acetyl-L-lysine deacetylase activity 16fold. High HDAC10 expression levels correlate with poor survival in children diagnosed with late-stage neuroblastoma
malfunction
a lysosomal phenotype in neuroblastoma cells that has been previously associated with HDAC10 inhibition is not observed. Inhibition of HDAC10 tends to correlate with HDAC6 inhibition
physiological function
cationic polyamines such as spermidine and spermine are critical in all forms of life, as they regulate the function of biological macromolecules. Intracellular polyamine metabolism is regulated by reversible acetylation and dysregulated polyamine metabolism is associated with neoplastic diseases such as colon cancer, prostate cancer and neuroblastoma. Both HDAC10 and its product spermidine are known to promote cellular survival through autophagy
physiological function
Cationic polyamines such as spermidine and spermine are critical in all forms of life, as they regulate the function of biological macromolecules. Intracellular polyamine metabolism is regulated by reversible acetylation. Both HDAC10 and its product spermidine are known to promote cellular survival through autophagy
physiological function
HDAC10 and spermidine act as mediators of autophagy
physiological function
HDAC10 and spermidine act as mediators of autophagy
physiological function
downregulation of HDAC10 significantly facilitates HIV-1 replication and increases viral integrated DNA. HDAC10 interacts with the HIV-1 integrase (IN) and the region of residues from 55 to 165 in IN is required for HDAC10 binding. The interaction between HDAC10 and IN specifically decreases the interaction between IN and cellular protein lens epithelium-derived growth factor. The progeny virus infectivity is increased in the HDAC10 downregulated cells, but decreased in the HDAC10 overexpressed cells
physiological function
HDAC10 is a zinc-dependent polyamine deacetylase exhibiting maximal catalytic activity against N8-acetylspermidine. As an inducer of autophagy, HDAC10 protects cancer cells from the cytotoxic chemotherapy drug doxorubicin; however, knock-down or specific inhibition of HDAC10 renders cancer cells more susceptible to doxorubicin. Inhibition of HDAC10 also impedes drug efflux mechanisms and induces double-stranded breaks in neuroblastoma cells but not non-malignant cells
physiological function
eukaryotic HDAC10 is a highly specific cytosolic polyamine deacetylase that utilizes N8-acetylspermidine as a substrate
additional information
nucleophilic attack of Zn2+-bound water at the amide carbonyl group polarized by Zn2+ and the catalytic tyrosine is facilitated by a general base. The Zn2+ ion, tyrosine, and tandem histidine residues contribute to transition state stabilization in each deacetylase. Collapse of the tetrahedral intermediate requires a proton donor, and the second histidine of the tandem pair must serve as the general acid due to its proximity to the leaving amino group. Structure-function analysis of substrate specificity, overview
additional information
-
nucleophilic attack of Zn2+-bound water at the amide carbonyl group polarized by Zn2+ and the catalytic tyrosine is facilitated by a general base. The Zn2+ ion, tyrosine, and tandem histidine residues contribute to transition state stabilization in each deacetylase. Collapse of the tetrahedral intermediate requires a proton donor, and the second histidine of the tandem pair must serve as the general acid due to its proximity to the leaving amino group. Structure-function analysis of substrate specificity, overview
additional information
nucleophilic attack of Zn2+-bound water at the amide carbonyl group polarized by Zn2+ and the catalytic tyrosine is facilitated by a general base. The Zn2+ ion, tyrosine, and tandem histidine residues contribute to transition state stabilization in each deacetylase. Collapse of the tetrahedral intermediate requires a proton donor, and the second histidine of the tandem pair must serve as the general acid due to its proximity to the leaving amino group. Structure-function analysis of substrate specificity, overview
additional information
-
nucleophilic attack of Zn2+-bound water at the amide carbonyl group polarized by Zn2+ and the catalytic tyrosine is facilitated by a general base. The Zn2+ ion, tyrosine, and tandem histidine residues contribute to transition state stabilization in each deacetylase. Collapse of the tetrahedral intermediate requires a proton donor, and the second histidine of the tandem pair must serve as the general acid due to its proximity to the leaving amino group. Structure-function analysis of substrate specificity, overview
additional information
two conserved structural motifs direct the narrow substrate specificity: a 310 helix containing the P(E,A)CE motif that sterically constricts the active site, and an electrostatic gatekeeper, E274, that confers selectivity for cationic polyamine substrates
additional information
tertiary structural features govern the substrate specificity of zHDAC10
additional information
critical for substrate recognition is a negatively charged glutamate (Glu272 hHDAC10 resp. Glu274 in drHDAC10) at the entrance of the active site, which acts as a gatekeeper to favor the binding of protonated and hence positively charged polyamine substrates
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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). Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PDB
SCOP
CATH
UNIPROT
ORGANISM
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified enzyme in complex with tubastatin A, oxa-tubastatin A, (1-[[4-(hydroxycarbamoyl)phenyl]methyl]-1H-indol-3-yl)-N,N-dimethylmethanaminium, 2-(1-[[4-(hydroxycarbamoyl)phenyl]methyl]-1H-indol-3-yl)-N,N-dimethylethan-1-aminium, N-hydroxy-4-[[3-(2-hydroxyethyl)-1H-indol-1-yl]methyl]benzamide, and N-hydroxy-4-[(1H-indol-1-yl)methyl]benzamide, sitting drop vapor diffusion method, X-ray diffraction structure determination and analysis at 2.0-2.65 A resolution, molecular replacement using the atomic coordinates of the Y307F HDAC10-trifluoromethylketone complex (PDB ID 5TD7) as a search probe
purified enzyme zHDAC10 mutant Y307F complexed with a polyamine transition state analogue inhibitor AAT, sitting drop vapour diffusion method, mixing of 400 nl of 30 mg/ml Y307F zHDAC10DELTA-AAT complex and 5 mM AAT with 400 nl of precipitant solution containing 0.2 M KH2PO4, and 20% PEG 3350, and equilibration against 0.08 ml precipitant solution, 24 h, 4°C, X-ray diffraction structure determination and analysis at 2.85 A resolution, molecular replacement using structure of the zHDAC6 CD1-TSA complex (PDB ID 5EEF)
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A24E/D94A
site-directed mutagenesis, the two amino acid substitutions in zebrafish HDAC10 yield an active site contour more similar to that of human HDAC10. The active site of A24E-D94A zebrafish HDAC10 thus mimics the active site of human HDAC10
E274L
Y307F
site-directed mutagenesis, introduction of the deactivating Y307F mutation facilitates crystallization
additional information
E274L
site-directed mutagenesis, steady-state kinetics, mutation of the glutamate gatekeeper residue
E274L
site-directed mutagenesis, the E274L substitution diminishes N8-acetylspermidine deacetylase activity 20fold and increases acetyl-L-lysine deacetylase activity 100fold
additional information
construction of deletion mutant DELTAnuA2, steady-state kinetics. The universal 310 helix nuA2 insertion in loop L1 further constricts the HDAC10 active site. Generation of mutant zHDAC10DELTA by treatement with trypsin
additional information
-
construction of deletion mutant DELTAnuA2, steady-state kinetics. The universal 310 helix nuA2 insertion in loop L1 further constricts the HDAC10 active site. Generation of mutant zHDAC10DELTA by treatement with trypsin
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pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
recombinant TEV-cleavable N-terminal His-MBP-tagged enzyme from Escherichia coli strain BL21(DE3) by amylose affinity chromatography and anion exchange chromatography, the MBP-tag is not cleaved off
recombinant TEV-cleavable N-terminal His-MBP-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by amylose affinity chromatography, TEV protease is used to remove the His-MBP-tag, followed by anion exchange chromatography and gel filtration
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene hdac10, DNA and amino acid sequence determination and analysis, sequence comparisons, recombinant expression of TEV-cleavable N-terminal His-MBP-tagged enzyme from codon-optimized HDAC10 gene (residues 2-675) in Escherichia coli strain BL21(DE3), expression of wild-type and mutant enzymes
gene HDAC10, DNA and amino acid sequence determination and analysis, sequence comparisons, recombinant expression of TEV-cleavable N-terminal His-MBP-tagged enzyme from codon-optimized HDAC10 gene in Escherichia coli strain BL21(DE3)
recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3), subcloning in Escherichia coli strain DH5alpha
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
medicine
pharmacology
HDAC10 isozyme-selective inhibitors will suppress autophagic responses to cancer chemotherapy, thereby rendering cancer cells more susceptible to cytotoxic drugs
drug development
HDAC10 is a biomarker and a target for the design of isozyme-selective inhibitors that will suppress autophagic responses to cancer chemotherapy, thereby rendering cancer cells more susceptible to cytotoxic drugs
drug development
HDAC10 has been linked to tumor development and proliferation. The development of potential drugs that block HDAC10 is a therapeutic strategy for the treatment of cancer, e.g. neuroblastoma lung cancer, ovarian cancer, and leukemia
medicine
downregulation of HDAC10 significantly facilitates HIV-1 replication and increases viral integrated DNA. HDAC10 interacts with the HIV-1 integrase (IN) and the region of residues from 55 to 165 in IN is required for HDAC10 binding. The interaction between HDAC10 and IN specifically decreases the interaction between IN and cellular protein lens epithelium-derived growth factor, leading to the inhibition of viral integration
medicine
given that high HDAC10 expression levels correlate with poor survival in children diagnosed with late-stage neuroblastoma, HDAC10 is emerging as a possible target for cancer chemotherapy
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
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Acetylspermidine deacetylase activities in human organs
Med. Sci. Res.
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1987
Homo sapiens
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brenda
Wang, Z.; Fries, D.; Blankenship, J.
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Mus musculus
brenda
Menezes, A.M.S.; Blankenship, J.
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36
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1993
Rattus sp.
brenda
Huang, T.L.; Dredar, S.A.; Manneh, V.A.; Blankenship, J.W.; Fries, D.S.
Inhibition of N8-acetylspermidine deacetylase by active-site-directed metal coordination inhibitiors
J. Med. Chem.
35
2414-2418
1992
Rattus sp.
brenda
Marchant, P.; Manneh, V.A.; Blankenship, J.
N1-Acetylspermidine is not a substrate for N-acetylspermidine deacetylase
Biochim. Biophys. Acta
881
297-299
1986
Rattus sp.
brenda
Manneh, V.A.; Blankenship, J.
Inhibitor studies on the characteristics of the active site of rat liver N8-acetylspermidine deacetylase
Proc. West. Pharmacol. Soc.
28
255-258
1985
Rattus sp.
-
brenda
Libby, P.R.
Acetylspermidine deacetylase (rat liver)
Methods Enzymol.
94
329-331
1983
Rattus sp.
brenda
Santacroce, M.J.; Blankenship, J.
Inhibition of acetylspermidine deacetylating activity from rat liver
Proc. West. Pharmacol. Soc.
25
113-118
1982
Rattus sp.
brenda
Blankenship, J.
Deacetylation of N8-acetylspermidine by subcellular fractions of rat tissue
Arch. Biochem. Biophys.
189
20-27
1978
Rattus sp.
brenda
Libby, P.R.
Properties of an acetylspermidine deacetylase from rat liver
Arch. Biochem. Biophys.
188
360-363
1978
Rattus sp.
brenda
Decroos, C.; Bowman, C.M.; Christianson, D.W.
Synthesis and evaluation of N8-acetylspermidine analogues as inhibitors of bacterial acetylpolyamine amidohydrolase
Bioorg. Med. Chem.
21
4530-4540
2013
Mycoplana ramosa
brenda
Shinsky, S.A.; Christianson, D.W.
Polyamine deacetylase structure and catalysis prokaryotic acetylpolyamine amidohydrolase and eukaryotic HDAC10
Biochemistry
57
3105-3114
2018
Homo sapiens (Q969S8), Homo sapiens, Danio rerio (F1QCV2), Danio rerio
brenda
Hai, Y.; Shinsky, S.A.; Porter, N.J.; Christianson, D.W.
Histone deacetylase 10 structure and molecular function as a polyamine deacetylase
Nat. Commun.
8
15368
2017
Homo sapiens (Q969S8), Homo sapiens, Danio rerio (F1QCV2), Danio rerio
brenda
Herbst-Gervasoni, C.J.; Steimbach, R.R.; Morgen, M.; Miller, A.K.; Christianson, D.W.
Structural basis for the selective inhibition of HDAC10, the cytosolic polyamine deacetylase
ACS Chem. Biol.
15
2154-2163
2020
Danio rerio (F1QCV2)
brenda
Osko, J.D.; Roose, B.W.; Shinsky, S.A.; Christianson, D.W.
Structure and function of the acetylpolyamine amidohydrolase from the deep earth halophile Marinobacter subterrani
Biochemistry
58
3755-3766
2019
Danio rerio (F1QCV2)
brenda
Herp, D.; Ridinger, J.; Robaa, D.; Shinsky, S.A.; Schmidtkunz, K.; Yesiloglu, T.Z.; Bayer, T.; Steimbach, R.R.; Herbst-Gervasoni, C.J.; Merz, A.; Romier, C.; Sehr, P.; Gunkel, N.; Miller, A.K.; Christianson, D.W.; Oehme, I.; Sippl, W.; Jung, M.
First fluorescent acetylspermidine deacetylation assay for HDAC10 identifies selective inhibitors with cellular target engagement
ChemBioChem
23
e202200180
2022
Danio rerio (F1QCV2)
brenda
Ran, X.; Ao, Z.; Olukitibi, T.; Yao, X.
Characterization of the role of host cellular factor histone deacetylase 10 during HIV-1 replication
Viruses
12
28
2019
Homo sapiens (Q969S8)
brenda
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