Information on EC 4.3.2.2 - adenylosuccinate lyase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea

EC NUMBER
COMMENTARY
4.3.2.2
-
RECOMMENDED NAME
GeneOntology No.
adenylosuccinate lyase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
(S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate = fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
show the reaction diagram
-
-
-
-
(S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate = fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
show the reaction diagram
kinetic and catalytic uni-bi rapid equilibrium ordered mechanism, key role for the conserved Ser298 in catalysis and pivotal role of the substrate in the activation of the catalytic base, detailed overview
O15918, -
(S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate = fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
show the reaction diagram
uni-bi mechanism, where fumarate is removed by beta-elimination via a general base-general acid mechanism
-
N6-(1,2-dicarboxyethyl)AMP = fumarate + AMP
show the reaction diagram
-
-
-
-
N6-(1,2-dicarboxyethyl)AMP = fumarate + AMP
show the reaction diagram
uni bi-ordered mechanism
-
N6-(1,2-dicarboxyethyl)AMP = fumarate + AMP
show the reaction diagram
kinetic and catalytic mechanism, the enzyme follows a rapid equilibrium ordered bi-uni mechanism in the reverse direction in which AMP binds first to the enzyme followed by fumarate, key role for the conserved Ser298 in catalysis and pivotal role of the substrate in the activation of the catalytic base, detailed overview
O15918, -
N6-(1,2-dicarboxyethyl)AMP = fumarate + AMP
show the reaction diagram
uni-bi mechanism, where fumarate is removed by beta-elimination via a general base-general acid mechanism
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
beta-elimination
P0AB89
-
beta-elimination
Q9X0I0
-
beta-elimination
-
-
beta-elimination
-
-
elimination
-
-
C-N bond cleavage
-
PATHWAY
KEGG Link
MetaCyc Link
adenosine ribonucleotides de novo biosynthesis
-
Alanine, aspartate and glutamate metabolism
-
Biosynthesis of secondary metabolites
-
inosine-5'-phosphate biosynthesis I
-
inosine-5'-phosphate biosynthesis II
-
inosine-5'-phosphate biosynthesis III
-
Metabolic pathways
-
Purine metabolism
-
SYSTEMATIC NAME
IUBMB Comments
N6-(1,2-dicarboxyethyl)AMP AMP-lyase (fumarate-forming)
Also acts on 1-(5-phosphoribosyl)-4-(N-succinocarboxamide)-5-aminoimidazole.
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
adenylosuccinase
-
-
-
-
adenylosuccinate lyase
-
-
adenylosuccinate lyase
-
-
adenylosuccinate lyase
-
-
ADSL
P30566
-
ADSL
-
-
AMPS lyase
-
-
-
-
ASASE
-
-
-
-
ASL
-
-
-
-
ASL
P12047
-
ASL
Q8X737
-
Glutamyl-tRNA synthetase regulatory factor
-
-
-
-
lyase, adenylosuccinate
-
-
-
-
succino AMP-lyase
-
-
-
-
succino-AMP lyase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9027-81-0
-
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
malfunction
-
adenylosuccinate lyase deficiency causes encephalopathy with epilepsy and marked psychomotor retardation
malfunction
-
phenotypic severity in ADSL deficiency is correlated with residual enzymatic activity and structural stability of the corresponding mutant ADSL complexes and does not result from genotype-specific disproportional catalytic activities toward one of the enzyme substrates
malfunction
-
a defect in the colonization phenotype is attributed to the disruption in adenylosuccinate lyase
malfunction
-
ADSL deficiency is an autosomal recessive disorder, characterized by severe neurologic involvement including seizures, developmental delay, hypotonia, and autistic features
malfunction
-
adenylosuccinate lyase deficiency is characterized by the accumulation of 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide and succinyladenosine in tissue and body fluids
physiological function
-
adenylosuccinate lyase is required for rhizosphere colonization in Pantoea agglomerans
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(Nomega-L-arginino)succinate
fumarate + L-arginine
show the reaction diagram
-
-
-
-
?
(S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
show the reaction diagram
-
-
-
-
?
(S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido
show the reaction diagram
-
-
-
-
?
(S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido
show the reaction diagram
-
-
-
-
?
(S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido
show the reaction diagram
P0AB89
-
-
-
?
(S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido
show the reaction diagram
-
-
-
-
?
(S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido
show the reaction diagram
Q9X0I0
-
-
-
?
(S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido
show the reaction diagram
-
-
-
-
?
1-(5-phosphoribosyl)-4-(N-succinocarboxamide)-5-aminoimidazole
5'-phosphoribosyl-5-amino-4-imidazolecarboxamide
show the reaction diagram
-
-
-
?
1-(5-phosphoribosyl)-4-(N-succinocarboxamide)-5-aminoimidazole
5'-phosphoribosyl-5-amino-4-imidazolecarboxamide
show the reaction diagram
-
i.e. 4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide ?
-
-
?
2',3'-dideoxyadenylosuccinate
dideoxyadenosine 5'-monophosphate + ?
show the reaction diagram
-
at 1.44% of the activity with the natural substrate
-
?
2'-deoxy-succino-AMP
2'-deoxy-AMP + ?
show the reaction diagram
-
-
-
?
2'-deoxy-succino-AMP
2'-deoxy-AMP + ?
show the reaction diagram
-
-
-
?
4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
?
show the reaction diagram
-
reaction in the biosynthesis of AMP
-
-
-
4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
?
show the reaction diagram
-
reaction in the biosynthesis of AMP
-
-
-
4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
?
show the reaction diagram
-
reaction in the biosynthesis of AMP
-
-
-
4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
?
show the reaction diagram
-
enzyme catalyzes two nonsequential reactions in purine biosynthesis
-
-
-
5-aminoimidazole-(N-succinylocarboxamide) ribotide
5-aminoimidazole-4-carboxamide ribotide + fumarate
show the reaction diagram
-
-
-
-
?
5-aminoimidazole-(N-succinylocarboxamide) ribotide
5-aminoimidazole-4-carboxamide ribotide + fumarate
show the reaction diagram
-
-
-
-
?
5-aminoimidazole-(N-succinylocarboxamide) ribotide
5-aminoimidazole-4-carboxamide ribotide + fumarate
show the reaction diagram
P0AB89
-
-
-
?
5-aminoimidazole-(N-succinylocarboxamide) ribotide
5-aminoimidazole-4-carboxamide ribotide + fumarate
show the reaction diagram
-
-
-
-
?
5-aminoimidazole-(N-succinylocarboxamide) ribotide
5-aminoimidazole-4-carboxamide ribotide + fumarate
show the reaction diagram
Q9X0I0
-
-
-
?
5-aminoimidazole-(N-succinylocarboxamide) ribotide
5-aminoimidazole-4-carboxamide ribotide + fumarate
show the reaction diagram
-
-
-
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
-
-
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
-
-
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
-
-
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
-
-
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
-
-
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-, P12047
-
-
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-, Q8X737
-
-
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
-
ZMP accumulation in the brain of Lesch-Nyhan disease patients induces inhibition of mitochondrial oxidative phosphorylation and adenylosuccinate lyase activity, followed by dowregulation of ATP levels and multifocal cell death in the cerebellum. ZMP is an inhibitor of the bifunctional enzyme adenylosuccinate lyase, a deficiency of this enzyme causes psychomotor and mental retardation in humans, overview, i.e. AICAR or ZMP
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
O15918, -
first step common to both de novo and the salvage pathways in purine biosynthesis
-
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
i.e. SAICAR
i.e. AICAR
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
i.e. SAICAR
i.e. AICAR
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
P30566
i.e. SAICAR
i.e. AICAR
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-, P12047
i.e. SAICAR
i.e. AICAR
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
the 8th step in the purine nucleotide de novo pathway
-
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
O15918, -
i.e. SAICAR, SAICAR synthesis in vitro
i.e. AICAR
-
r
8-aza-succino-AMP
8-aza-AMP + ?
show the reaction diagram
-
-
-
?
adenylosuccinate
AMP + fumarate
show the reaction diagram
-
-
-
-
?
adenylosuccinate
AMP + fumarate
show the reaction diagram
-
-
-
-
?
adenylosuccinate
AMP + fumarate
show the reaction diagram
-
-
-
-
?
adenylosuccinate
adenosine monophosphate + fumarate
show the reaction diagram
-
-
-
-
?
adenylosuccinate
adenosine monophosphate + fumarate
show the reaction diagram
-
-
-
-
?
adenylosuccinate
adenosine monophosphate + fumarate
show the reaction diagram
P0AB89
-
-
-
?
adenylosuccinate
adenosine monophosphate + fumarate
show the reaction diagram
-
-
-
-
?
adenylosuccinate
adenosine monophosphate + fumarate
show the reaction diagram
Q9X0I0
-
-
-
?
adenylosuccinate
adenosine monophosphate + fumarate
show the reaction diagram
-
-
-
-
?
adenylosuccinate 2',3'-acyclic dialcohol
?
show the reaction diagram
-
-
-
-
?
adenylosuccinate 2',3'-acyclic dialdehyde
?
show the reaction diagram
-
-
-
?
arabinosyl-succino-AMP
arabinosyl-AMP + ?
show the reaction diagram
-
-
-
?
arabinosyl-succino-AMP
arabinosyl-AMP + ?
show the reaction diagram
-
i.e. beta-D-arabinosyladenylosuccinate
beta-D-arabinosyl-AMP
?
fumarate + AMP
N6-(1,2-dicarboxyethyl)AMP
show the reaction diagram
-
-
-
r
fumarate + AMP
N6-(1,2-dicarboxyethyl)AMP
show the reaction diagram
-
-
-
r
fumarate + AMP
N6-(1,2-dicarboxyethyl)AMP
show the reaction diagram
-
-
-
r
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
-
-
-
-
?
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
-
-
-
-
?
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
P0AB89
-
-
-
?
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
-
-
-
-
?
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
Q9X0I0
-
-
-
?
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
-
-
-
-
?
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
-
i.e. adenylosuccinate
-
-
?
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
-
i.e. adenylosuccinate
-
?
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
-
i.e. adenylosuccinate
-
?
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
-
i.e. adenylosuccinate
-
-
?
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
-
i.e. adenylosuccinate
-
-
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
-
i.e. adenylosuccinate
-
r
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
-
i.e. adenylosuccinate
-
-
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
-
i.e. adenylosuccinate
-
r
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
-
i.e. adenylosuccinate
-
r
N6-(1,2-dicarboxyethyl)AMP
?
show the reaction diagram
-
enzyme catalyzes the last step in the pathway of AMP biosynthesis
-
-
-
N6-(1,2-dicarboxyethyl)AMP
?
show the reaction diagram
-
reaction in the biosynthesis of AMP
-
-
-
N6-(1,2-dicarboxyethyl)AMP
?
show the reaction diagram
-
reaction in the biosynthesis of AMP
-
-
-
N6-(1,2-dicarboxyethyl)AMP
?
show the reaction diagram
-
reaction in the biosynthesis of AMP
-
-
-
N6-(1,2-dicarboxyethyl)AMP
?
show the reaction diagram
-
terminal step in AMP biosynthesis
-
-
-
succino-4-aminopyrazolo[3,4-d]pyrimidine ribose 5'-phosphate
4-aminopyrazolo[3,4-d]pyrimidine ribose 5'-phosphate + ?
show the reaction diagram
-
-
-
?
succinyladenosine monophosphate
AMP + fumarate
show the reaction diagram
-
-
-
-
?
succinyladenosine monophosphate
AMP + fumarate
show the reaction diagram
-
-
-
-
?
succinyladenosine monophosphate
AMP + fumarate
show the reaction diagram
P30566
-
-
-
?
succinyladenosine monophosphate
AMP + fumarate
show the reaction diagram
-
-
-
-
?
succinyladenosine monophosphate
AMP + fumarate
show the reaction diagram
O15918, -
-
-
-
?
succinyladenosine monophosphate
AMP + fumarate
show the reaction diagram
-
-
-
-
?
succinyladenosine monophosphate
AMP + fumarate
show the reaction diagram
-, P12047
-
-
-
?
succinyladenosine monophosphate
AMP + fumarate
show the reaction diagram
-, Q8X737
-
-
-
?
succinyladenosine monophosphate
AMP + fumarate
show the reaction diagram
-
conversion of adenylosuccinate to adenylate in the purine nucleotide cycle
-
-
?
succinyladenosine monophosphate
AMP + fumarate
show the reaction diagram
O15918, -
second step common to both de novo and the salvage pathways in purine biosynthesis
-
-
?
mercaptopurinosuccinate
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
the low activity of the enzyme in liver of severely starved rats is inconsistent with the proposal that the purine nucleotide cycle plays a major role in ammonia production for urea synthesis at least under these conditions
-
-
-
additional information
?
-
-
roles of adenylosuccinate lyase and of AMP deaminase in the anti-HIV activity of 2',3'-dideoxyadenosine and 2',3'-dideoxyinosine
-
-
-
additional information
?
-
-
adenylosuccinate lyase catalyzes two reactions in the biosynthesis of purine nucleotides
-
-
-
additional information
?
-
P30566
adenylosuccinate lyase catalyzes two reactions in the biosynthesis of purine nucleotides
-
-
-
additional information
?
-
P30566
adenylosuccinate lyase deficiency is a rare autosomal disorder of de novo purine synthesis, which results in the accumulation of succinylpurines in body fluids. Patients with adenylosuccinate lyase deficiency show a variable combination of mental retardation, epilepsy and autistic features, overview
-
-
-
additional information
?
-
-
adenylosuccinate lyase deficiency is an autosomal recessive disorder of the purine de novo synthesis pathway and purine nucleotide cycleby severe neurological involvement including hypotonia, seizures, developmental delay and autistic features. Epilepsy in ADSL deficiency is frequent and occurs in approximately two-thirds of patients, beginning either early in the neonatal period or after the first year of life
-
-
-
additional information
?
-
O15918, -
adenylosuccinate lyase is the only enzyme in the purine biosynthetic pathway that catalyzes two distinct, but chemically similar reactions
-
-
-
additional information
?
-
-
ZMP is an activator of the AMP-activated protein kinase, AMPK, and is toxic in human B lymphocytes and neuroblastoma cell lines, physiological functions of ZMP, overview
-
-
-
additional information
?
-
P30566
residue Ser289 is essential for catalysis
-
-
-
additional information
?
-
-
residues Ser262 and Ser263 in a flexible loop of the enzyme are essential for catalysis
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide
show the reaction diagram
-
-
-
-
?
(S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido
show the reaction diagram
-
-
-
-
?
(S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido
show the reaction diagram
-
-
-
-
?
(S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido
show the reaction diagram
P0AB89
-
-
-
?
(S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido
show the reaction diagram
-
-
-
-
?
(S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido
show the reaction diagram
Q9X0I0
-
-
-
?
(S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
fumarate + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido
show the reaction diagram
-
-
-
-
?
4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
?
show the reaction diagram
-
reaction in the biosynthesis of AMP
-
-
-
4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
?
show the reaction diagram
-
reaction in the biosynthesis of AMP
-
-
-
4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
?
show the reaction diagram
-
reaction in the biosynthesis of AMP
-
-
-
4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
?
show the reaction diagram
-
enzyme catalyzes two nonsequential reactions in purine biosynthesis
-
-
-
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
-
-
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
-
-
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
-
-
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
-
-
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
-
-
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-, P12047
-
-
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-, Q8X737
-
-
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
-
ZMP accumulation in the brain of Lesch-Nyhan disease patients induces inhibition of mitochondrial oxidative phosphorylation and adenylosuccinate lyase activity, followed by dowregulation of ATP levels and multifocal cell death in the cerebellum. ZMP is an inhibitor of the bifunctional enzyme adenylosuccinate lyase, a deficiency of this enzyme causes psychomotor and mental retardation in humans, overview
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
O15918, -
first step common to both de novo and the salvage pathways in purine biosynthesis
-
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
i.e. SAICAR
i.e. AICAR
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
P30566
i.e. SAICAR
i.e. AICAR
-
?
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
the 8th step in the purine nucleotide de novo pathway
-
-
?
adenylosuccinate
AMP + fumarate
show the reaction diagram
-
-
-
-
?
adenylosuccinate
AMP + fumarate
show the reaction diagram
-
-
-
-
?
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
-
-
-
-
?
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
-
-
-
-
?
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
P0AB89
-
-
-
?
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
-
-
-
-
?
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
Q9X0I0
-
-
-
?
N6-(1,2-dicarboxyethyl)AMP
fumarate + AMP
show the reaction diagram
-
-
-
-
?
N6-(1,2-dicarboxyethyl)AMP
?
show the reaction diagram
-
enzyme catalyzes the last step in the pathway of AMP biosynthesis
-
-
-
N6-(1,2-dicarboxyethyl)AMP
?
show the reaction diagram
-
reaction in the biosynthesis of AMP
-
-
-
N6-(1,2-dicarboxyethyl)AMP
?
show the reaction diagram
-
reaction in the biosynthesis of AMP
-
-
-
N6-(1,2-dicarboxyethyl)AMP
?
show the reaction diagram
-
reaction in the biosynthesis of AMP
-
-
-
N6-(1,2-dicarboxyethyl)AMP
?
show the reaction diagram
-
terminal step in AMP biosynthesis
-
-
-
succinyladenosine monophosphate
AMP + fumarate
show the reaction diagram
-
-
-
-
?
succinyladenosine monophosphate
AMP + fumarate
show the reaction diagram
-
-
-
-
?
succinyladenosine monophosphate
AMP + fumarate
show the reaction diagram
P30566
-
-
-
?
succinyladenosine monophosphate
AMP + fumarate
show the reaction diagram
-
-
-
-
?
succinyladenosine monophosphate
AMP + fumarate
show the reaction diagram
-, P12047
-
-
-
?
succinyladenosine monophosphate
AMP + fumarate
show the reaction diagram
-, Q8X737
-
-
-
?
succinyladenosine monophosphate
AMP + fumarate
show the reaction diagram
-
conversion of adenylosuccinate to adenylate in the purine nucleotide cycle
-
-
?
succinyladenosine monophosphate
AMP + fumarate
show the reaction diagram
O15918, -
second step common to both de novo and the salvage pathways in purine biosynthesis
-
-
?
adenylosuccinate
AMP + fumarate
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
the low activity of the enzyme in liver of severely starved rats is inconsistent with the proposal that the purine nucleotide cycle plays a major role in ammonia production for urea synthesis at least under these conditions
-
-
-
additional information
?
-
-
roles of adenylosuccinate lyase and of AMP deaminase in the anti-HIV activity of 2',3'-dideoxyadenosine and 2',3'-dideoxyinosine
-
-
-
additional information
?
-
-
adenylosuccinate lyase catalyzes two reactions in the biosynthesis of purine nucleotides
-
-
-
additional information
?
-
P30566
adenylosuccinate lyase catalyzes two reactions in the biosynthesis of purine nucleotides
-
-
-
additional information
?
-
P30566
adenylosuccinate lyase deficiency is a rare autosomal disorder of de novo purine synthesis, which results in the accumulation of succinylpurines in body fluids. Patients with adenylosuccinate lyase deficiency show a variable combination of mental retardation, epilepsy and autistic features, overview
-
-
-
additional information
?
-
-
adenylosuccinate lyase deficiency is an autosomal recessive disorder of the purine de novo synthesis pathway and purine nucleotide cycleby severe neurological involvement including hypotonia, seizures, developmental delay and autistic features. Epilepsy in ADSL deficiency is frequent and occurs in approximately two-thirds of patients, beginning either early in the neonatal period or after the first year of life
-
-
-
additional information
?
-
O15918, -
adenylosuccinate lyase is the only enzyme in the purine biosynthetic pathway that catalyzes two distinct, but chemically similar reactions
-
-
-
additional information
?
-
-
ZMP is an activator of the AMP-activated protein kinase, AMPK, and is toxic in human B lymphocytes and neuroblastoma cell lines, physiological functions of ZMP, overview
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
KCl
-
stimulates up to maximum concentration of 80 mM, inhibition at higher concentration
PO43-
-
activates at low concentration, inhibits at high concentrations above 25 mM
SO42-
-
activates at low concentrations, inhibits at concentrations above 25 mM
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
2'-deoxy-AMP
-
-
2'-deoxy-AMP
-
competitive
4-aminopyrazolo[3,4-d]pyrimidine ribose 5'-phosphate
-
-
5-aminoimidazole-4-carboxamide ribonucleoside
O15918, -
50% inhibition at 0.167 mM
5-aminoimidazole-4-carboxamide riboside 5'-monophosphate
-
i.e. ZMP or AICAR, product inhibition, accumulation in the brain of Lesch-Nyhan disease patients induces inhibition of mitochondrial oxidative phosphorylation and adenylosuccinate lyase activity, followed by dowregulation of ATP levels and multifocal cell death in the cerebellum
adenosine phosphonobutyric acid, 2'(3'),5'-diphosphate
-
i.e. APBADP, the non-cleavable substrate analogue acts as a competitive inhibitor with respect to either substrate. ASL binds up to 4 mol of APBADP per mole of enzyme tetramer, the enzyme exhibits negative cooperativity. Binding to enzyme mutants, overview
adenosine phosphonobutyric acid, 2'(3'),5'-diphosphate
-
i.e. APBADP, the non-cleavable substrate analogue acts as a competitive inhibitor with respect to either substrate. ASL binds up to 4 mol of APBADP per mole of enzyme tetramer, the enzyme exhibits positive cooperativity
adenyloethylphosphonate
-
-
adenylophosphonobutyrate
-
-
-
adenylosuccinate 2',3'-acyclic (N,N-ethyl) diamine
-
weak
adenylosuccinate 2',3'-acyclic dialcohol
-
-
adenylosuccinate 2',3'-acyclic dialdehyde
-
-
ADP
-
weak, competitive
ammonium salt of N6-malonyl adenosine 5'-phosphate
-
noncompetitive inhibitor, irreversible
AMP
-
competitive
AMP
-
competitive
AMP
O15918, -
product inhibition competitive versus succinyladenosine monophosphate
arabinosyl-AMP
-
-
arabinosyl-AMP
-
beta-D-arabinosyl-AMP, competitive
ATP
-
weak, competitive
DL-3-phosphonoalanine
-
-
EDTA
-
above 15 mM
erythro-beta-fluoro-4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
-
-
erythro-beta-fluoroadenylosuccinate
-
-
erythro-beta-fluoroaspartate
-
-
fumarate
-
noncompetitive
fumarate
-
noncompetitive
fumarate
-
noncompetitive
I-
-
100-200 mM
KBr
-, P12047
presence of increasing concentrations of KBr of 0.12.5 M disrupt electrostatic interactions leading to ASL dissociation and loss of catalytic activity
KCl
-
stimulates up to maximum concentration of 80 mM, inhibition at higher concentration
mercaptopurinosuccinate
-
substrate inhibition
Mg2+
-
concentration of Mg2+ approaching that of EDTA
N-(5-amino-1-(beta-D-ribofuranosyl)imidazole-4-carbonyl)-L-threo-beta-methylaspartic acid 5'-phosphate
-
-
-
N6-(2-carboxyethyl)-AMP
-
i.e. adenylopropionate
N6-(D-1,2-dicarboxyethyl)-AMP
-
i.e. D-adenylosuccinate
N6-(D-1,2-dicarboxypropyl)-AMP
-
i.e. adenyloglutarate
-
N6-(DL-1,2-dicarboxy-threo-2-hydroxyethyl)-AMP
-
i.e. adenylomalate
N6-(DL-1-carboxy-2-phosphonoethyl)AMP
-
i.e. adenylophosphonopropionate
N6-(L-1-carboxy-2-cyanoethyl)-AMP
-
i.e. adenylocyanopropionate
N6-(L-1-carboxy-2-methylsulfoxyethyl)-AMP
-
i.e. adenylomethylsulfoxypropionate
N6-(L-1-carboxy-2-nitroethyl)-AMP
-
competitive
N6-(L-1-carboxy-2-sulfinoethyl)-AMP
-
i.e. adenylosulfinopropionate
N6-(L-1-carboxy-2-sulfoethyl)-AMP
-
i.e. adenylosulfopropionate
nitroacrylate
-
0.02 mM, 70% inactivation
NO3-
-
100-200 mM
phosphate
-
competitive
phosphopropionoadenosine
-
-
-
PO43-
-
activates at low concentration, inhibits at high concentrations above 25 mM
SO42-
-
activates at low concentrations, inhibits at concentrations above 25 mM
threo-beta-4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
-
-
-
threo-beta-fluoroadenylosuccinate
-
-
trans-4-hydroxy-2-nonenal
-
10-15 M, inhibitor reacts both with the free enzyme and the enzme substrate complex
virazole 5'-phosphate
-
-
additional information
-
dithiothreitol increases inhibition of trans-4-hydroxy-2-nonenal; hydroxylamine reverses inhibition of trans-4-hydroxy-2-nonenal
-
additional information
-, P12047
as hydrophobic interactions are weakened at 8C and 4C, the catalytic activity of ASL decreases strikingly and the enzyme dissociates to a mixture of monomer-dimer-trimer, with small amounts of tetramer
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0437
-
2',3'-dideoxyadenylosuccinate
-
-
0.0008
-
2'-deoxy-succino-AMP
-
-
0.003
-
2'-deoxy-succino-AMP
-
-
0.001
-
4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
-
-
0.0081
-
4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
-
-
0.0003
-
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
-
pH 7.0, 25C, mutant S290A
0.0016
-
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
-
pH 7.0, 25C, wild-type enzyme
0.0029
-
5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide
-
pH 7.0, 25C, wild-type enzyme
0.0095
-
8-aza-succino-AMP
-
-
0.00146
-
adenylosuccinate
-
histidine-tagged enzyme
0.0015
-
adenylosuccinate
-
mutant D69E
0.00177
-
adenylosuccinate
-
wild-type enzyme
0.00178
-
adenylosuccinate
-
none-tagged enzyme
0.0021
-
adenylosuccinate
-
wild-type enzyme
0.00224
-
adenylosuccinate
-
mutant S94A
0.0027
-
adenylosuccinate
-
wild type, 50 mM HEPES, pH 7.0, 25C
0.0071
-
adenylosuccinate
-
mutant R310K
0.0093
-
adenylosuccinate
-
mutant D69N
0.0128
-
adenylosuccinate
-
mutant S306A
0.0177
-
adenylosuccinate
-
mutant T93A
0.0192
-
adenylosuccinate
-
mutant T140A
0.023
-
adenylosuccinate
-
mutant R310Q
0.0013
-
adenylsuccinate
-
mutant D69E, 50 mM HEPES, pH 7.0, 25C
0.002
-
adenylsuccinate
-
mutant D65R/D69E, 50 mM HEPES, pH 7.0, 25C
0.004
-
adenylsuccinate
-
50 mM HEPES, pH 7.0, 25C
0.0043
-
adenylsuccinate
-
mutant I62E/D69E, 50 mM HEPES, pH 7.0, 25C
0.0046
-
adenylsuccinate
-
mutant D65R, 50 mM HEPES, pH 7.0, 25C
0.0061
-
adenylsuccinate
-
mutant I62E/D65R/D69E, 50 mM HEPES, pH 7.0, 25C
0.0107
-
adenylsuccinate
-
mutant I62D/D65R/D69E, 50 mM HEPES, pH 7.0, 25C
0.0166
-
adenylsuccinate
-
mutant Q212E, 50 mM HEPES, pH 7.0, 25C
0.0175
-
adenylsuccinate
-
mutant I62E, 50 mM HEPES, pH 7.0, 25C
0.0177
-
adenylsuccinate
-
mutant I62D/D69E, 50 mM HEPES, pH 7.0, 25C
0.0181
-
adenylsuccinate
-
mutant I62E/D65R, 50 mM HEPES, pH 7.0, 25C
0.0488
-
adenylsuccinate
-
mutant I62D/D65R, 50 mM HEPES, pH 7.0, 25C
0.0551
-
adenylsuccinate
-
mutant I62D, 50 mM HEPES, pH 7.0, 25C
0.034
-
AMP
O15918, -
pH 7.4, 25C
0.036
-
AMP
-
-
0.0027
-
arabinosyl-succino-AMP
-
-
0.0056
-
arabinosyl-succino-AMP
-
-
0.035
-
fumarate
-
-
0.76
-
fumarate
O15918, -
pH 7.4, 25C
0.0012
-
N6-(1,2-dicarboxyethyl)AMP
-
-
0.0015
-
N6-(1,2-dicarboxyethyl)AMP
-
-
0.00254
-
N6-(1,2-dicarboxyethyl)AMP
-
enzyme from cell line 1751
0.00289
-
N6-(1,2-dicarboxyethyl)AMP
-
enzyme from cell line 1753
0.0033
-
N6-(1,2-dicarboxyethyl)AMP
-
-
0.0033
-
N6-(1,2-dicarboxyethyl)AMP
-
enzyme from wild-type cell lines
0.0047
-
N6-(1,2-dicarboxyethyl)AMP
-
-
0.012
-
N6-(1,2-dicarboxyethyl)AMP
-
-
0.013
-
N6-(1,2-dicarboxyethyl)AMP
-
-
0.011
-
succino-4-aminopyrazolo[3,4-d]pyrimidine ribose 5'-phosphate
-
-
0.032
-
succinyladenosine monophosphate
O15918, -
pH 7.4, 25C
-
0.02
-
mercaptopurinosuccinate
-
-
additional information
-
additional information
-
pH-dependence of Km-value
-
additional information
-
additional information
O15918, -
thermodynamics and kinetics, initial velocity and transient kinetics of succinyladenosine monophosphate cleavage, overview
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.00048
-
adenylosuccinate
-
mutant T140A
0.00689
-
adenylosuccinate
-
mutant S306A
0.01
-
adenylosuccinate
-
mutant T93A
1.14
-
adenylosuccinate
-
mutant S94A
1.74
-
adenylosuccinate
-
wild-type enzyme
2.9
-
AMP
O15918, -
pH 7.4, 25C
7.5
-
succinyladenosine monophosphate
O15918, -
pH 7.4, 25C
-
2.9
-
fumarate
O15918, -
pH 7.4, 25C
additional information
-
additional information
-
pH-dependence of turnover-numbers
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.16
-
adenosine phosphonobutyric acid, 2'(3'),5'-diphosphate
-
inhibition kinetics, overview
0.21
-
adenosine phosphonobutyric acid, 2'(3'),5'-diphosphate
-
inhibition kinetics, overview
0.093
-
AMP
O15918, -
pH 7.4, 25C
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
8.3e-05
-
-
mutant R310Q, pH 7.0
0.004
-
P0AB89
mutant S295A, pH 7.0
0.008
-
P0AB89
mutant H171N, pH 7.0
0.009
-
P0AB89
mutant H171A, pH 7.0
0.031
-
P0AB89
mutant H171A, pH 8.5
0.04
-
P0AB89
mutant H171N, pH 8.5
0.04
-
-
mutant D69N, pH 7.0
0.063
-
-
mutant I62D/D65R, adenylsuccinate, 50 mM HEPES, pH 7.0, 25C
0.068
-
-
complementation of inactive mutant ASLs, maximum specific activity, T93A + H141Q, 3.0% wild-type activity
0.069
-
-
mutant I62D/D65R, succinylaminoimidazole carboxamide, 50 mM HEPES, pH 7.0, 25C
0.072
-
-
mutant I62D/D65R/D69E, adenylsuccinate, 50 mM HEPES, pH 7.0, 25C
0.094
-
-
mutant I62D/D65R/D69E, succinylaminoimidazole carboxamide, 50 mM HEPES, pH 7.0, 25C
0.096
-
-
complementation of inactive mutant ASLs, maximum specific activity, S306A + H141Q, 4.6% wild-type activity
0.1
-
-
mutant R310K, pH 7.0
0.18
-
-
mutant I62D/D65R + I62E/D65R/D69E, adenylsuccinate, 50 mM HEPES, pH 7.0, 25C
0.2
-
-, P12047
wild-type enzyme at 4 mg/ml and 4C
0.21
-
-
complementation of inactive mutant ASLs, maximum specific activity, T93A + K268Q, 10.1% wild-type activity
0.24
-
-
mutant I62D/D65R + I62E/D65R/D69E, succinylaminoimidazole carboxamide, 50 mM HEPES, pH 7.0, 25C
0.24
-
-
complementation of inactive mutant ASLs, maximum specific activity, T140A + H68Q, 11.5% wild-type activity
0.32
-
-
complementation of inactive mutant ASLs, maximum specific activity, S306A + K268Q, 15.4% wild-type activity; complementation of inactive mutant ASLs, maximum specific activity, T140A + K268Q, 15.4% wild-type activity
0.33
-
-
mutant I62E/D65R/D69E, adenylsuccinate, 50 mM HEPES, pH 7.0, 25C
0.4
-
-
crude cell lysate
0.4
-
-
mutant D69E, pH 7.0
0.4
-
-, P12047
wild-type enzyme at 4 mg/ml and 8C
0.46
-
-
mutant I62E/D65R/D69E, succinylaminoimidazole carboxamide, 50 mM HEPES, pH 7.0, 25C
0.53
-
-
mutant I62E/D65R/D69E, succinylaminoimidazole carboxamide, 50 mM HEPES, pH 7.0, 25C
0.54
-
-
mutant I62E/D65R, adenylsuccinate, 50 mM HEPES, pH 7.0, 25C
0.97
-
-
mutant I62E/D65R/D69E, adenylsuccinate + succinylaminoimidazole carboxamide, 50 mM HEPES, pH 7.0, 25C
1
-
-
mutant R396H, pH 7.4, 25C
1.07
-
-
adenylsuccinate and succinylaminoimidazole carboxamide, 50 mM HEPES, pH 7.0, 25C
1.09
-
-
mutant I62D/D65R, adenylsuccinate + succinylaminoimidazole carboxamide, 50 mM HEPES, pH 7.0, 25C
1.1
-
-
mutant R396H, after treatment with guanidiniumHCl, pH 7.4, 25C
1.29
-
-
mutant I62D/D65R + I62E/D65R/D69E, adenylsuccinate + succinylaminoimidazole carboxamide, 50 mM HEPES, pH 7.0, 25C
1.3
-
-
mutant I62D/D65R/D69E, adenylsuccinate + succinylaminoimidazole carboxamide, 50 mM HEPES, pH 7.0, 25C
1.4
-
-
mutant I62E/D65R/D69E, adenylsuccinate + succinylaminoimidazole carboxamide, 50 mM HEPES, pH 7.0, 25C
1.58
-
-
adenylsuccinate, 50 mM HEPES, pH 7.0, 25C
1.6
-
-
mutant R396C, after treatment with guanidiniumHCl, pH 7.4, 25C
1.7
-
-
succinylaminoimidazole carboxamide, 50 mM HEPES, pH 7.0, 25C
1.7
-
-, P12047
wild-type enzyme at 4 mg/ml and 25C
1.75
-
-
wild-type enzyme, pH 7.0
1.8
-
-
mutant R396C, pH 7.4, 25C
2.4
-
-
-
3.6
-
-
final purified human enzyme; imidazole gradient elution
3.8
-
-
non tagged enzyme
4.65
-
P0AB89
wild-type protein, pH 7.0
7.5
-
-
His-tagged mutant L311V, after treatment with guanidiniumHCl, pH 7.4, 25C
7.8
-
-
His-tagged mutant L311V, pH 7.4, 25C
8.3
-
-
His-tagged wild-type, after treatment with guanidiniumHCl, pH 7.4, 25C
8.4
-
-
wild-type, after treatment with guanidiniumHCl, pH 7.4, 25C
8.5
-
-
His-tagged wild-type, pH 7.4, 25C
8.6
-
-
wild-type, pH 7.4, 25C
8.7
-
-
His-tagged mutant R194C, pH 7.4, 25C
8.9
-
-
His-tagged mutant R194C, after treatment with guanidiniumHCl, pH 7.4, 25C
16.47
-
P0AB89
wild-type protein, pH 8.5
additional information
-
-
-
additional information
-
-
-
additional information
-
-
complementation of inactive mutant ASLs, maximum specific activity, T140A + H141Q, T93A + H68Q, S306A + H68Q 0% wild-type activity
additional information
-
-, P12047
specific activities of different enzyme variants with different subunit numbers
additional information
-
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.9
-
-
synthesis of N6-(1,2-dicarboxyethyl)AMP
7
-
-
cleavage of N6-(1,2-dicarboxyethyl)AMP
7
-
P0AB89
activity assay
7
-
-
activity assay
7
-
-, P12047
assay at
7.4
-
-
activity assay
7.4
-
O15918, -
assay at
7.7
8.7
-
Tris buffer
7.8
-
-
all cell lines examined
8
8.5
-
-
8.5
-
P0AB89
activity assay
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.8
9
O15918, -
-
6
9.5
-
inactive below pH 6 and above 9.5
7.2
8.4
-
-
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
P0AB89
activity assay
25
-
-
activity assay
25
-
-, P12047
assay at
25
-
O15918, -
assay at
37
-
O15918, -
reverse reaction SAICAR synthesis
PDB
SCOP
CATH
ORGANISM
Bacillus subtilis (strain 168)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Escherichia coli (strain K12)
Francisella tularensis subsp. tularensis (strain SCHU S4 / Schu 4)
Legionella pneumophila subsp. pneumophila (strain Philadelphia 1 / ATCC 33152 / DSM 7513)
Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)
Plasmodium vivax (strain Salvador I)
Plasmodium vivax (strain Salvador I)
Pyrobaculum aerophilum (strain ATCC 51768 / IM2 / DSM 7523 / JCM 9630 / NBRC 100827)
Staphylococcus aureus (strain MW2)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Thermotoga maritima (strain ATCC 43589 / MSB8 / DSM 3109 / JCM 10099)
Trypanosoma brucei brucei (strain 927/4 GUTat10.1)
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
52000
-
Q9X0I0
monomer
57000
-
-
histidine-tagged enzyme, determined by SDS-PAGE
147000
-
-
determined by native polyacrylamide gel electrophoresis, wild-type enzyme
148000
-
-
determined by native polyacrylamide gel electrophoresis, mutant R310K
152000
-
-
mutant N270L, light scattering measurements, 0.2 mg/ml enzyme in a filtered 20 mM potassium phosphate buffer at pH 7.0, containing 20 mM potassium chloride
153000
-
-
wild type, light scattering measurements, 0.2 mg/ml enzyme in a filtered 20 mM potassium phosphate buffer at pH 7.0, containing 20 mM potassium chloride
155000
-
-
mutant D69E, light scattering method, 0.25 mg/ml
159000
-
-
mutant Q212E, light scattering measurements, 0.2 mg/ml enzyme in a filtered 20 mM potassium phosphate buffer at pH 7.0, containing 20 mM potassium chloride
159000
-
-
mutant I62E/D65R/D69E, light scattering method, 0.25 mg/ml
166000
-
-
mutant N270D, light scattering measurements, 0.2 mg/ml enzyme in a filtered 20 mM potassium phosphate buffer at pH 7.0, containing 20 mM potassium chloride
173000
-
-
mutant R301K, light scattering measurements, 0.2 mg/ml enzyme in a filtered 20 mM potassium phosphate buffer at pH 7.0, containing 20 mM potassium chloride
173000
-
-
mutant I62E, light scattering method, 0.25 mg/ml
174000
-
-
mutant Q212M, light scattering measurements, 0.2 mg/ml enzyme in a filtered 20 mM potassium phosphate buffer at pH 7.0, containing 20 mM potassium chloride
176000
-
-
mutant I62D, light scattering method, 0.25 mg/ml
176000
-
-
determined by light scattering, mutant D69N
181000
-
-
light scattering method, 0.25 mg/ml
182000
-
-
determined by light scattering, mutant R310K
191000
-
-
determined by light scattering, wild-type enzyme
191000
-
-
wild-type enzyme, light scattering
192000
-
-
mutant S263H, light scattering
193000
-
-
determined by native polyacrylamide gel electrophoresis, mutant S93A
194000
-
-
determined by light scattering, mutant D69E
194000
-
-
determined by native polyacrylamide gel electrophoresis, mutant T93A
194800
-
-
determined by analytical ultracentrifugation, mutant T140A
196000
-
-
wild-type enzyme, gel filtration
196000
-
-
determined by native polyacrylamide gel electrophoresis, wild-type enzyme
196000
-
-
mutant S262A, light scattering
197000
-
-
mutant S263A, light scattering
199000
-
-
mutant S262H, light scattering
199700
-
-
determined by analytical ultracentrifugation, wild-type enzyme
200000
-
-
gel filtration
200000
-
-
gel filtration
200000
-
-
-
200000
-
-
SDS-PAGE
200000
-
-, Q8X737
gel filtration
201000
-
-
mutant enzyme S413P, gel filtration
209000
-
-
mutant I62E/D65R, native PAGE
210000
-
-
native PAGE
216400
-
-
determined by analytical ultracentrifugation, mutant S306A
217000
-
-
mutant I62D/D65R, native PAGE
219000
-
-
mutant R301Q, light scattering measurements, 0.2 mg/ml enzyme in a filtered 20 mM potassium phosphate buffer at pH 7.0, containing 20 mM potassium chloride
221000
-
-
mutant S290H, light scattering
222000
-
-
analytical ultracentrifugation
223000
-
-
gel filtration, at 22C
227000
-
-
wild-type enzyme and mutant S289H, light scattering
227000
-
-
analytical ultracentrifugation, at 37C
228000
-
-
gel filtration, His-tagged protein
230000
-
-
analytical ultracentrifugation, at 25C
234000
-
-
mutant I62D/D65R/D69E, light scattering method, 0.25 mg/ml
234000
-
-
mutant S290A, light scattering
237000
-
-
mutant S289A, light scattering
300000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 49490, calculation from nucleotide sequence
?
-
x * 56000, SDS-PAGE
?
-
x * 55000, calculation from nucleotide sequence
?
B2LS18, -
x * 54552, calculated
homodimer
-
2 * 50000, SDS-PAGE
homotetramer
-
4 * 50000, SDS-PAGE
homotetramer
P0AB89
-
homotetramer
-
-
homotetramer
-, Q8X737
x-ray crystallography
homotetramer
-
4 * 56000, analytical ultracentrifugation; 4 * 57000, SDS-PAGE
tetramer
-
4 * 52000, SDS-PAGE
tetramer
-
4 * 50000, SDS-PAGE
tetramer
-
-
tetramer
-, P12047
a homotetramer in which three subunits contribute to each of four active sites, analytical ultracentrifugation, gel filtration, circular dichroism spectroscopy, and interaction analysis, overview. ASL is active and exists as 100% tetramer at 25C, while at 8C and 4C, as hydrophobic interactions are weakened, the catalytic activity decreases strikingly and the enzyme dissociates to a mixture of monomer-dimer-trimer, with small amounts of tetramer. In the presence of increasing concentrations of KBr of 0.12.5 M, which disrupts electrostatic interactions, ASL is dissociated initially to monomerdimer, with small amounts of trimer-tetramer, and then the monomer species predominates along with small amounts of trimer-tetramer, analytical ultracentrifugation, homology modelling of wild-type and mutant enzymes, overview
tetramer
O15918, -
4 * 55000, recombinant His-tagged enzyme, SDS-PAGE, 4 * 56235, recombinant His-tagged enzyme, mass spectrometry
tetramer
Q7A0G9, -
4 * 49600, calculated. Enzyme forms a dimer of dimers, crystallization data
tetramer
-
4 * 57000, calculated, His-tagged protein
additional information
-
enzyme is composed of 6-8 identical subunits
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
hanging drop vapor diffusion method, using 1.4 M sodium/potassium phosphate pH 7.5 and 4% (v/v) glycerol
-, Q8X737
the crystal structures of wild-type ADL, and mutant-substrate, H171A-ADS, and -product, H171N-AMP-FUM, complexes are determined to 2.0, 1.85, and 2.0 A resolution, respectively
P0AB89
at a resolution of 2.1 A
-
in complex with AMP, at 2.5 A resolution, and modeling of oxalate in the active site. Comparisons with the enzyme from Escherichia coli and with human PurB show close similarity of the active sites, but differences in the way that the subunits are assembled into dimers
Q7A0G9, -
at a resolution of 1.8 A
Q9X0I0
TEMPERATURE STABILITY
TEMPERATURE STABILITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
-
enzyme is stable for at least 5 days at 25C, and upon rapid freezing and thawing
37
-
-
t1/2 for enzyme from mutant cell line 1751: 0.23 min, t1/2 for enzyme from mutant cell line 1753: 0.2 min, t1/2 for enzyme from the normal cell lines: 9.65 h
50
-
-
at 50C the wild type enzyme shows 79-84% of the activity at 25C
60
-
-
t1/2 for enzyme from mutant cell line 1751: 7.35 h, t1/2 for enzyme from mutant cell line 1753: 6.25 h, t1/2 for enzyme from the normal lines: 2.18 min
60
-
-
wild type and mutant enzymes R396H and R396C are relatively stable at 60C for about 4 h, the R194C mutant enzyme loses most of its activity within about 1 h of incubation at 60 C
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
dialysis for 24 h at 5C, activity in mutant lysates is decreased by 95% while 50-60% of the initial activity remains in the normal cell lysates
-
freezing at -80C, followed by thawing, 20-40% loss of enzyme activity in extract
-
unstable to quick freezing in dry ice/acetone
-
stable to thawing and refreezing at a protein concentration of above 2 mg/ml
-
three cycles of freezing and thawing remove nearly all enzyme activity
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-70C, 10% glycerol, 1 mM dithiothreitol, 0.01 M Tris, pH 7.4, activity in lysates from all cell lines is stable for more than 6 weeks
-
-80C or -20C, recombinant enzyme is very unstable regardless of salt or glycerol concentration
-
-80C, potassium phosphate buffer, KCl, DTT, EDTA, glycerol
-
-70C, unstable to storage
-
2C or -20C, stable for two months
-
4C, stable for several weeks
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
Ni-affinity chromatography
-
recombinant His6-tagged wild-type and mutant enzymes from Escherichia coli strain Bl21 by nickel affinity chromatography
-, P12047
using nickel affinity chromatography
-
using nickel nitrilotriacetic acid-agarose
-
Q-Sepharose column chromatography and gel filtration
-, Q8X737
using a Ni-NTA column
P0AB89
Ni-NTA agarose column chromatography
-
normal and mutant enzyme S413P
-
using a Ni-NTA column, the 6-histidine tag is removed by cleavage with thrombin, separation of thrombin and histidine-tag from the enzyme is achieved by using a Sephadex G-100 column
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli as His tag enzymes
-
expression of His6-tagged wild-type and mutant enzymes in Escherichia coli strain BL21
-, P12047
for expression in Escherichia coli BL21DE3 cells
-
for expression in Escherichia coli strain BL21DE3
-
expression in Escherichia coli
B2LS18, -
expressed in Escherichia coli BL21(DE3) cells
-, Q8X737
subcloned from the pUC118 into the pET28a vector for expression in Escherichia coli B834DE3 cells
P0AB89
ADSL gene, genotyping in Polish patients with adenylosuccinate lyase deficiency compared to the wild-type, overview
-
expressed in Escherichia coli DH5alphaF'IQ cells as recombinant maltose binding protein-ADSL fusion protein
-
expressed in Escherichia coli Rosetta 2 (DE3) cells
-
expression in Escherichia coli
-
into the pET-14b vector for expression in Escherichia coli Rosetta 2DE3pLysS cells
-
normal and mutant enzyme S413P, expression in Escherichia coli
-
expression of wild-type and mutant enzymes in Escherichia coli strain DH5alpha
O15918, -
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
D65R
-
mutant with differences in thermal stability, catalytic activity and substrate binding
D65R/D69E
-
mutant with differences in thermal stability, catalytic activity and substrate binding
D69E
-
mutant with differences in thermal stability, catalytic activity and substrate binding
D69E
-
mutant exibits an increase in its pK2
D69N
-
mutant exibits a decrease in its pK2
D69N
-
site-directed mutagenesis, the mutant shows altered binding of inhibitory substrate analogue adenosine phosphonobutyric acid, 2'(3'),5'-diphosphate compared to the wild-type enzyme
E239M
-, P12047
site-directed mutagenesis, the mutant shows reduced Vmax, increased Km, and lower molecular weight compared to the wild-type enzyme, subunit structure analysis
E239Q
-, P12047
site-directed mutagenesis, the mutant shows reduced Vmax, increased Km, and lower molecular weight compared to the wild-type enzyme, subunit structure analysis
E239R
-, P12047
site-directed mutagenesis, the mutant shows reduced Vmax, increased Km, and lower molecular weight compared to the wild-type enzyme, subunit structure analysis
H141Q
-
site-directed mutagenesis, the mutant shows altered binding of inhibitory substrate analogue adenosine phosphonobutyric acid, 2'(3'),5'-diphosphate compared to the wild-type enzyme
H299K
-, P12047
site-directed mutagenesis, the mutant shows reduced Vmax, increased Km, and lower molecular weight compared to the wild-type enzyme, subunit structure analysis
H299R
-, P12047
site-directed mutagenesis, the mutant shows reduced Vmax, increased Km, and lower molecular weight compared to the wild-type enzyme, subunit structure analysis
H68A
-
site-directed mutagenesis, the mutant shows altered binding of inhibitory substrate analogue adenosine phosphonobutyric acid, 2'(3'),5'-diphosphate compared to the wild-type enzyme
H89Q
-
site-directed mutagenesis, the mutant shows altered binding of inhibitory substrate analogue adenosine phosphonobutyric acid, 2'(3'),5'-diphosphate compared to the wild-type enzyme
H89R
-
site-directed mutagenesis, the mutant shows altered binding of inhibitory substrate analogue adenosine phosphonobutyric acid, 2'(3'),5'-diphosphate compared to the wild-type enzyme
I62D
-
mutant with differences in thermal stability, catalytic activity and substrate binding
I62D/D65R
-
mutant with differences in thermal stability, catalytic activity and substrate binding
I62D/D65R/D69E
-
mutant with differences in thermal stability, catalytic activity and substrate binding
I62D/D69E
-
mutant with differences in thermal stability, catalytic activity and substrate binding
I62E
-
mutant with differences in thermal stability, catalytic activity and substrate binding
I62E/D65R
-
'humanized' normal enzyme
I62E/D65R/D69E
-
mutant with differences in thermal stability, catalytic activity and substrate binding
I62E/D69E
-
mutant with differences in thermal stability, catalytic activity and substrate binding
N270D
-
mutant with impaired activity
N270L
-
mutant with impaired activity
Q212E
-
mutant with impaired activity
Q212M
-
mutant with impaired activity
R167E
-, P12047
site-directed mutagenesis, the mutant shows reduced Vmax, increased Km, and lower molecular weight compared to the wild-type enzyme, subunit structure analysis
R167Q
-, P12047
site-directed mutagenesis, the mutant shows reduced Vmax, increased Km, and lower molecular weight compared to the wild-type enzyme, subunit structure analysis
R301K
-
mutant with impaired activity
R301Q
-
mutant with impaired activity
R310K
-
mutant shows little change in pK2
R310Q
-
mutant exibits a decrease in its pK2
S262A
-
site-directed mutagenesis, the mutant shows no activity and altered molecular weight compared to the wild-type enzyme
S262H
-
site-directed mutagenesis, the mutant shows no activity and altered molecular weight compared to the wild-type enzyme
S263A
-
site-directed mutagenesis, the mutant shows no activity and altered molecular weight compared to the wild-type enzyme
S263H
-
site-directed mutagenesis, the mutant shows no activity and altered molecular weight compared to the wild-type enzyme
S306A
-
conserved amino acid in all adenylosuccinate lyases, mutant for testing the involvement of the residue in the enzyme function
S94A
-
conserved amino acid in all adenylosuccinate lyases, mutant for testing the involvement of the residue in the enzyme function
T140A
-
conserved amino acid in all adenylosuccinate lyases, mutant for testing the involvement of the residue in the enzyme function
T93A
-
conserved amino acid in all adenylosuccinate lyases, mutant for testing the involvement of the residue in the enzyme function
H171A
P0AB89
mutant to map out the residues involved in adenylosuccinate binding, and to identify the putative catalytic groups
H171N
P0AB89
mutant to map out the residues involved in adenylosuccinate binding, and to identify the putative catalytic groups
S295A
P0AB89
mutant to probe the role of S295 in the catalytic mechanism
A260GfsX24
-
the mutation is associated with ADSL deficiency
D215H
-
naturally occuring mutation, two homozygous and two compound heterozygous mutant variants
D215H
-
the mutation is associated with ADSL deficiency and shows 92% activity using 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide as substrate at 25C compared to the wild type enzyme
D268H
-
naturally occuring mutation, two homozygous and two compound heterozygous mutant variants
D268H
-
the mutation is associated with ADSL deficiency and shows 20% activity using 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide as substrate at 25C compared to the wild type enzyme
D422Y
-
mutant without enzyme activity
D430N
-
mutant without enzyme activity
D430N
-
the mutation is associated with ADSL deficiency and shows 151% activity using 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide as substrate at 25C compared to the wild type enzyme
D87E
-
the mutation is associated with ADSL deficiency and shows 91% activity using 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide as substrate at 25C compared to the wild type enzyme
E376D
-
the mutation is associated with ADSL deficiency and shows 49% activity using 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide as substrate at 25C compared to the wild type enzyme
E80D
-
the mutation is associated with ADSL deficiency and shows 102% activity using 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide as substrate at 25C compared to the wild type enzyme
E80D/D87E
-
australian patient with autism
I351T
-
naturally occuring mutation, two homozygous and two compound heterozygous mutant variants
I351T
-
the mutation is associated with ADSL deficiency and shows 151% activity using 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide as substrate at 25C compared to the wild type enzyme
K246E
-
the mutation is associated with adenylosuccinate lyase deficiency, the Vmax for the K246E mutant enzyme is about 2% that of the wild type enzyme, K246E exists mainly as dimer or monomer
L311V
-
the mutation is associated with adenylosuccinate lyase deficiency, the Vmax for the L311V mutant enzyme is 72% about 2% that of the wild type enzyme
L311V
-
about 90% of wild-type actitivy
P100A/D422Y
-
the mutation leads to a defective enzyme which is inhibited by micromolar concentrations of trans-4-hydroxy-2-nonenal
P110A/D422Y
-
heat sensitive mutant
R141W
-
thermostable mutant with decreased activity
R149G
-
the mutation is associated with ADSL deficiency
R190Q
-
the mutation is associated with ADSL deficiency and shows 119% activity using 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide as substrate at 25C compared to the wild type enzyme
R194C
-
the mutation is associated with adenylosuccinate lyase deficiency,Vmax (at 25C) for R194C is comparable to that of wild type, R194C is rapidly inactivated at 60C
R194C
-
the mutation is associated with ADSL deficiency and shows 101% activity using 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide as substrate at 25C compared to the wild type enzyme
R194C
-
about 100% of wild-type actitivy
R303C
-
thermostable mutant with decreased activity
R396C
-
the mutation is associated with adenylosuccinate lyase deficiency the Vmax for the R396C mutant enzyme is about 16% that of the wild type enzyme
R396C
-
the mutation is associated with ADSL deficiency and shows 32% activity using 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide as substrate at 25C compared to the wild type enzyme
R396C
-
about 20% of wild-type actitivy
R396H
-
the mutation is associated with adenylosuccinate lyase deficiency, Vmax (at 25C) for R194C is considerably reduced and affinity for adenylosuccinate is retained
R396H
-
about 10% of wild-type actitivy
R426H
-
mutant without enzyme activity
R426H
-
naturally occuring mutation, two homozygous and two compound heterozygous mutant variants
R426H
-
the mutation is associated with ADSL deficiency and shows 89% activity using 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide as substrate at 25C compared to the wild type enzyme
S23R
-
naturally occuring mutation, two homozygous and two compound heterozygous mutant variants
S23R
-
the mutation is associated with ADSL deficiency and shows 108% activity using 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide as substrate at 25C compared to the wild type enzyme
S289A
-
site-directed mutagenesis, the mutant shows no activity, and altered molecular weight and binding of inhibitory substrate analogue adenosine phosphonobutyric acid, 2'(3'),5'-diphosphate compared to the wild-type enzyme
S289H
-
site-directed mutagenesis, the mutant shows no activity, and altered molecular weight and binding of inhibitory substrate analogue adenosine phosphonobutyric acid, 2'(3'),5'-diphosphate compared to the wild-type enzyme
S290A
-
site-directed mutagenesis, the mutant shows altered molecular weight and binding of inhibitory substrate analogue adenosine phosphonobutyric acid, 2'(3'),5'-diphosphate compared to the wild-type enzyme
S290H
-
site-directed mutagenesis, the mutant shows no activity, and altered molecular weight and binding of inhibitory substrate analogue adenosine phosphonobutyric acid, 2'(3'),5'-diphosphate compared to the wild-type enzyme
S395R
-
thermostable mutant with decreased activity
S413P
-
the mutation leads to structural instability of the mutant enzyme, this instability lowers the enzyme level in lymphocytes. The mutation segregates with mental retardation in the affected family
S438P
-
heat sensitive mutant without enzyme activity
T242I
-
naturally occuring mutation, two homozygous and two compound heterozygous mutant variants
T242I
-
the mutation is associated with ADSL deficiency and shows 108% activity using 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide as substrate at 25C compared to the wild type enzyme
T450S
-
the mutation is associated with ADSL deficiency and shows 68% activity using 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide as substrate at 25C compared to the wild type enzyme
Y114H
-
naturally occuring mutation, two homozygous and two compound heterozygous mutant variants
Y114H
-
the mutation is associated with ADSL deficiency and shows 37% activity using 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide as substrate at 25C compared to the wild type enzyme
S298A
O15918, -
site-directed mutagenesis, the mutation does not lead to gross changes in the structural properties of ASL, but the specific activity of S298A mutant is 1000fold lower than that of the wild enzyme, the specific activity remains unchanged upon variation of pH
S298C
O15918, -
site-directed mutagenesis, the mutation does not lead to gross changes in the structural properties of ASL, but the activity of the S298C mutant is completely lost
L423V
-
mutant without enzyme activity
additional information
-
the review gives an overview of the characteristics of patients with ADSL deficiency in dependence of amino acid changes
additional information
P30566
enzyme deficiency due to homozygous missense mutation T674C leading to the amino acid exchange M225T in the exon 6 of the ADSL gene causes a phenotype with global developmental delay, motor apraxia, severe speech deficits, seizures and behavioural features, which combines excessive laughter, a very happy disposition, hyperactivity, a short attention span, the mouthing of objects, tantrums and stereotyped movements that give a behavioural profile mimicking Angelman syndrome, the patients have an increased succinyladenosine/5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide ratio of 1.6 compared to wild-type humans, overview
additional information
-
genotype is related to severity of the mental retardation phenotype, overview
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
adenylosuccinate lyase deficiency causes serious neurological and physiological symptoms
additional information
-
participates in the purine biosynthetic pathway, enzyme defects result in psychomotor retardation, epilepsy, muscle wasting and autistic features
medicine
-
generation of in vitro hybrids that mimic compound heterozygote ASL for studies on disease-associated mutant enzymes. His-tagged wild-type/non-His-tagged wild-type, His-tagged wild-type/non-His-tagged R396C, His-tagged wild-type/non-His-tagged R396H, His-tagged R194C/non-His-tagged R396C, and His-tagged L311V/non-His-tagged R396H enzyme pairs are used in various hybrids generated by denaturing pairs of enzymes in 1 M guanidinium chloride and renaturing them by removing the denaturant. The hybrids have predominant amounts of heterotetramers. Analysis of the Vmax values of the hybrids indicates that most of the subunits behave independently. However, the hybrid tetramers retain weak positive cooperativity
additional information
-
participates in the purine biosynthetic pathway, enzyme defects result in psychomotor retardation, epilepsy, muscle wasting and autistic features
medicine
-
adenylosuccinate lyase deficiency causes serious neurological and physiological symptoms
additional information
-
participates in the purine biosynthetic pathway, enzyme defects result in psychomotor retardation, epilepsy, muscle wasting and autistic features