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
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
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
COMMENTARY
LITERATURE
beta-elimination
-
-
beta-elimination
-
-
beta-elimination
P0AB89
-
beta-elimination
-
-
beta-elimination
Q9X0I0
-
beta-elimination
-
-
elimination
-
-
C-N bond cleavage
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
adenosine ribonucleotides de novo biosynthesis
-
-
Alanine, aspartate and glutamate metabolism
-
-
Biosynthesis of antibiotics
-
-
Biosynthesis of secondary metabolites
-
-
inosine-5'-phosphate biosynthesis I
-
-
inosine-5'-phosphate biosynthesis II
-
-
inosine-5'-phosphate biosynthesis III
-
-
Metabolic pathways
-
-
Purine metabolism
-
-
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
COMMENTARY
LITERATURE
adenylosuccinase
-
-
-
-
adenylosuccinate lyase
-
-
adenylosuccinate lyase
-
-
adenylosuccinate lyase
-
-
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
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
4 normal cell lines: 894, 1707, 1502 and 1454, 2 cell lines from patients with infantile autism: 1751, 1753
-
-
Manually annotated by BRENDA team
gene ADSL
UniProt
Manually annotated by BRENDA team
normal and mutant enzyme S413P
-
-
Manually annotated by BRENDA team
Polish patients with adenylosuccinate lyase deficiency
-
-
Manually annotated by BRENDA team
Pyrobaculum aerophilum DSM 7523
-
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
the enzyme structurally resembles the enzymes of the aspartase/fumarase superfamily, conserved flexible C3 loop, phylogenetic analysis
evolution
A0R4I6
the enzyme structure adheres to the fold of the enzymes of the aspartase/fumarase superfamily, conserved flexible C3 loop, phylogenetic analysis
malfunction
-
a defect in the colonization phenotype is attributed to the disruption in adenylosuccinate lyase
malfunction
-
adenylosuccinate lyase deficiency causes encephalopathy with epilepsy and marked psychomotor retardation
malfunction
-
adenylosuccinate lyase deficiency is characterized by the accumulation of 5-aminoimidazole-4-(N-succinylcarboxamide) ribonucleotide and succinyladenosine in tissue and body fluids
malfunction
-
ADSL deficiency is an autosomal recessive disorder, characterized by severe neurologic involvement including seizures, developmental delay, hypotonia, and autistic features
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
-
ADSL enzyme deficiency is a disorder of purine metabolism with a broad clinical spectrum. The enzyme deficit causes a highly variable clinical presentation varying from a relatively mild presentation with slight motor retardation and severe muscle hypotonia to severe neonatal onset convulsions accompanied by severe mental retardation
malfunction
-
enzyme mutation R303C is involved in ADSL deficiency, a rare autosomal recessive disorder, which causes a defect in purine metabolism resulting in neurological and physiological symptoms. The R303C mutation potentially has a disproportional decrease in activity toward its substrates
malfunction
-
missense mutations in the protein lead to enzyme deficiency, an inborn error of purine metabolism characterized by neurological and physiological symptoms. Enzyme deficiency is biochemically diagnosed by elevated levels of succinylaminoimidazolecarboxamide riboside and succinyladenosine, the dephosphorylated derivatives of the substrates. Succinyladenosine/succinylaminoimidazolecarboxamide riboside ratios are associated with three phenotypic groups
metabolism
-
adenylosuccinate lyase is involved in the de novo purine biosynthesis pathway and purine nucleotide cycle
metabolism
-
the enzyme executes two non-sequential steps in the de novo synthesis of AMP: the conversion of phosphoribosylsuccinyl-aminoimidazole carboxamide to phosphoribosylaminoimidazole carboxamide, which occurs in the de novo synthesis of IMP, and the conversion of adenylosuccinate to AMP, which occurs in the de novo synthesis of AMP and also in the purine nucleotide cycle, using the same active site
physiological function
-
adenylosuccinate lyase is required for rhizosphere colonization in Pantoea agglomerans
physiological function
-
a housekeeping enzyme
physiological function
A0R4I6
a housekeeping enzyme
metabolism
-
the enzyme is a bifunctional protein that is involved in both purine de novo synthesis and purine interconversion. It catalyzes the formation of phosphoribosylaminoimidazole carboxamide and succinate from phosphoribosylsuccinyl-aminoimidazole carboxamide in the biosynthesis of IMP from phosphoribosylpyrophosphate. Alternatively, the enzyme catalyzes the synthesis of AMP and succinate from succinyl-AMP in the interconversion of IMP into AMP
additional information
-
homology modeling of the enzyme structure using the Mycobacterium smegmatis enzyme structure as a template, comparison to the human enzyme structure and other enzymes, structure-function relationship analysis based on the Mycobacterium smegmatis enzyme structure, active site residues, overview
additional information
A0R4I6
structure-function relationship analysis, active site residues, overview
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
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 ?
-
-
?
1-(5-phosphoribosyl)-4-(N-succinocarboxamide)-5-aminoimidazole
5'-phosphoribosyl-5-amino-4-imidazolecarboxamide + fumarate
show the reaction diagram
-
-
-
-
?
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 + fumarate
show the reaction diagram
-
-
-
?
2'-deoxy-succino-AMP
2'-deoxy-AMP + fumarate
show the reaction diagram
-
-
-
?
4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
reaction in the biosynthesis of AMP
-
-
-
4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
reaction in the biosynthesis of AMP
-
-
-
4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
reaction in the biosynthesis of AMP
-
-
-
4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
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
-
-
-
-
?
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-(N-succinylocarboxamide) ribotide
5-aminoimidazole-4-carboxamide ribotide + fumarate
show the reaction diagram
A0R4I6
-
-
-
?
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 + fumarate
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
adenylic 2',3'-acyclic dialcohol + fumarate
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
-
-
-
phosphoribosylsuccinyl-aminoimidazole carboxamide
phosphoribosylaminoimidazole carboxamide + fumarate
show the reaction diagram
-
-
-
-
?
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
-
-
-
-
r
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
A0R4I6
-
-
-
r
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
-
-
-
additional information
?
-
-
the activity of the Mycobacterium tuberculosis enzyme is particularly low
-
-
-
additional information
?
-
-
development of a rapid and simple HPLC-based assay method to quantitatively measure ADSL activity with succinyladenosine monophosphate in erythrocytes using isocratic ionpairing reversed-phase HPLC with UV-detection, overview
-
-
-
additional information
?
-
-
interaction between the enzyme and phosphoribosylsuccinyl-aminoimidazole carboxamide, isothermal titration calorimetry, overview. Modeling of AMPand phosphoribosylaminoimidazole carboxamide, and fumarate binding in the active site of wild-type and R303C mutant enzymes
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
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
-
-
-
-
?
1-(5-phosphoribosyl)-4-(N-succinocarboxamide)-5-aminoimidazole
5'-phosphoribosyl-5-amino-4-imidazolecarboxamide + fumarate
show the reaction diagram
-
-
-
-
?
4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
reaction in the biosynthesis of AMP
-
-
-
4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
reaction in the biosynthesis of AMP
-
-
-
4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
show the reaction diagram
-
reaction in the biosynthesis of AMP
-
-
-
4-(N-succino)-5-aminoimidazole-4-carboxamide ribonucleotide
5-aminoimidazole-4-carboxamide ribonucleotide + fumarate
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
A0R4I6
-
-
-
?
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
-
-
-
phosphoribosylsuccinyl-aminoimidazole carboxamide
phosphoribosylaminoimidazole carboxamide + fumarate
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
-
-
-
-
r
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
A0R4I6
-
-
-
r
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
-
-
-
additional information
?
-
-
the activity of the Mycobacterium tuberculosis enzyme is particularly low
-
-
-
METALS and IONS
ORGANISM
UNIPROT
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
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
8-Aza-AMP
-
-
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
CuSO4
-
complete inhibition at 0.05 mM
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]
SUBSTRATE
ORGANISM
UNIPROT
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
0.004
AMP
-
-
0.034
AMP
O15918
pH 7.4, 25C
0.036
AMP
-
-
0.0027
arabinosyl-succino-AMP
-
-
0.0056
arabinosyl-succino-AMP
-
-
0.035
fumarate
-
-
0.52
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
-
-
0.0007
phosphoribosylsuccinyl-aminoimidazole carboxamide
-
recombinant His-tagged mutant R426H, pH 7.4, 25C
-
0.00174
phosphoribosylsuccinyl-aminoimidazole carboxamide
-
recombinant His-tagged wild-type enzyme, pH 7.4, 25C
-
0.009
phosphoribosylsuccinyl-aminoimidazole carboxamide
-
recombinant His-tagged mutant R303C, pH 7.4, 25C
-
0.011
succino-4-aminopyrazolo[3,4-d]pyrimidine ribose 5'-phosphate
-
-
0.0014
succinyladenosine monophosphate
-
recombinant His-tagged mutant R426H, pH 7.4, 25C
0.0021
succinyladenosine monophosphate
-
recombinant His-tagged wild-type enzyme, pH 7.4, 25C
0.0027
succinyladenosine monophosphate
-
recombinant His-tagged mutant R303C, pH 7.4, 25C
0.0091
succinyladenosine monophosphate
-
wild-type enzyme, pH 8.1, 37C
0.032
succinyladenosine monophosphate
O15918
pH 7.4, 25C
0.0437
succinyladenosine monophosphate
A0R4I6
pH 7.6, 37C
0.2042
succinyladenosine monophosphate
-
pH 7.6, 37C
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
-
additional information
additional information
-
the enzyme shows cooperativity and does not follow simple Michaelis-Menten kinetics, kinetic analysis, overview
-
additional information
additional information
-
non-linear dependence of the activities on the substrate ratios due to competitive binding. The enzyme does not follow simple Michaelis-Menten kinetics, kinetic analysis of wild-type and mutant enzymes, overview. Wild-type enzyme and mutant R426H appear to have equivalent cooperative binding on both substrates, while mutant R303C demonstrates no cooperativity
-
additional information
additional information
A0R4I6
Michaelis-Menten kinetics
-
additional information
additional information
-
Michaelis-Menten kinetics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
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
0.1
succinyladenosine monophosphate
-
pH 7.6, 37C
0.7
succinyladenosine monophosphate
A0R4I6
pH 7.6, 37C
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
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3640
phosphoribosylsuccinyl-aminoimidazole carboxamide
-
recombinant His-tagged mutant R303C, pH 7.4, 25C
0
37500
phosphoribosylsuccinyl-aminoimidazole carboxamide
-
recombinant His-tagged mutant R426H, pH 7.4, 25C
0
50900
phosphoribosylsuccinyl-aminoimidazole carboxamide
-
recombinant His-tagged wild-type enzyme, pH 7.4, 25C
0
0.5
succinyladenosine monophosphate
-
pH 7.6, 37C
38527
16.02
succinyladenosine monophosphate
A0R4I6
pH 7.6, 37C
38527
915
succinyladenosine monophosphate
-
recombinant His-tagged mutant R303C, pH 7.4, 25C
38527
17800
succinyladenosine monophosphate
-
recombinant His-tagged mutant R426H, pH 7.4, 25C
38527
25200
succinyladenosine monophosphate
-
recombinant His-tagged wild-type enzyme, pH 7.4, 25C
38527
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
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]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.000083
-
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
6.4
-
purified recombinant His-tagged mutant R426H enzyme, substrate phosphoribosylsuccinyl-aminoimidazole carboxamide, pH 7.4, 25C
6.7
-
purified recombinant His-tagged mutant R426H enzyme, substrate succinyladenosine monophosphate, pH 7.4, 25C
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
13.9
-
purified recombinant His-tagged wild-type enzyme, substrate succinyladenosine monophosphate, pH 7.4, 25C
16.47
P0AB89
wild-type protein, pH 8.5
23.3
-
purified recombinant His-tagged wild-type enzyme, substrate phosphoribosylsuccinyl-aminoimidazole carboxamide, pH 7.4, 25C
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
ORGANISM
UNIPROT
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
7.4
-
assay at
7.7 - 8.7
-
Tris buffer
7.8
-
all cell lines examined
8 - 8.5
-
-
8.5
P0AB89
activity assay
8.5
Q8ZY28
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5.8 - 9
O15918
-
6 - 9.5
-
inactive below pH 6 and above 9.5
7.2 - 8.4
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
P0AB89
activity assay
25
-
activity assay
25
P12047
assay at
25
O15918
assay at
25
-
assay at
37
O15918
reverse reaction SAICAR synthesis
37
A0R4I6
assay at
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Pyrobaculum aerophilum DSM 7523
-
-
-
Manually annotated by BRENDA team
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)
Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720)
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
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
52000
Q9X0I0
monomer
681945
57000
-
histidine-tagged enzyme, determined by SDS-PAGE
682657
147000
-
determined by native polyacrylamide gel electrophoresis, wild-type enzyme
682733
148000
-
determined by native polyacrylamide gel electrophoresis, mutant R310K
682733
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
664041
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
664041
155000
-
mutant D69E, light scattering method, 0.25 mg/ml
665595
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
664041
159000
-
mutant I62E/D65R/D69E, light scattering method, 0.25 mg/ml
665595
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
664041
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
664041
173000
-
mutant I62E, light scattering method, 0.25 mg/ml
665595
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
664041
176000
-
mutant I62D, light scattering method, 0.25 mg/ml
665595
176000
-
determined by light scattering, mutant D69N
682733
181000
-
light scattering method, 0.25 mg/ml
665595
182000
-
determined by light scattering, mutant R310K
682733
191000
-
determined by light scattering, wild-type enzyme
682733
191000
-
wild-type enzyme, light scattering
695003
192000
-
mutant S263H, light scattering
695003
193000
-
determined by native polyacrylamide gel electrophoresis, mutant S93A
682738
194000
-
determined by light scattering, mutant D69E
682733
194000
-
determined by native polyacrylamide gel electrophoresis, mutant T93A
682738
194800
-
determined by analytical ultracentrifugation, mutant T140A
682738
196000
-
wild-type enzyme, gel filtration
34461
196000
-
determined by native polyacrylamide gel electrophoresis, wild-type enzyme
682738
196000
-
mutant S262A, light scattering
695003
197000
-
mutant S263A, light scattering
695003
199000
-
mutant S262H, light scattering
695003
199700
-
determined by analytical ultracentrifugation, wild-type enzyme
682738
200000
-
gel filtration
34449
200000
-
gel filtration
34451
200000
-
-
34454
200000
-
SDS-PAGE
664041
200000
Q8X737
gel filtration
706979
201000
-
mutant enzyme S413P, gel filtration
34461
209000
-
mutant I62E/D65R, native PAGE
665595
210000
-
native PAGE
665595
214500
-
recombinant His-tagged R303C mutant enzyme
729218
216400
-
determined by analytical ultracentrifugation, mutant S306A
682738
217000
-
mutant I62D/D65R, native PAGE
665595
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
664041
221000
-
mutant S290H, light scattering
695003
222000
-
analytical ultracentrifugation
682657
223000
-
gel filtration, at 22C
707497
225000
-
recombinant His-tagged wild-type enzyme
729218
227000
-
wild-type enzyme and mutant S289H, light scattering
695003
227000
-
analytical ultracentrifugation, at 37C
707497
228000
-
gel filtration, His-tagged protein
714232
230000
-
analytical ultracentrifugation, at 25C
707497
234000
-
mutant I62D/D65R/D69E, light scattering method, 0.25 mg/ml
665595
234000
-
mutant S290A, light scattering
695003
237000
-
mutant S289A, light scattering
695003
300000
-
gel filtration
1541
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 56000, SDS-PAGE
?
-
x * 55000, calculation from nucleotide sequence
?
-
x * 49490, calculation from nucleotide sequence
?
B2LS18
x * 54552, calculated
homodimer
-
2 * 50000, SDS-PAGE
homotetramer
-
-
homotetramer
P0AB89
-
homotetramer
-
4 * 50000, SDS-PAGE
homotetramer
-
4 * 57000, SDS-PAGE
homotetramer
Q8X737
x-ray crystallography
homotetramer
-
4 * 56000, analytical ultracentrifugation
homotetramer
-
recombinant His-tagged wild-type and R303C mutant enzymes, static light scattering
tetramer
-
-
tetramer
-
4 * 50000, SDS-PAGE
tetramer
-
4 * 52000, SDS-PAGE
tetramer
O15918
4 * 55000, recombinant His-tagged enzyme, SDS-PAGE, 4 * 56235, recombinant His-tagged enzyme, mass spectrometry
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
Q7A0G9
4 * 49600, calculated. Enzyme forms a dimer of dimers, crystallization data
tetramer
-
4 * 57000, calculated, His-tagged protein
homotetramer
A0R4I6
the enzyme forms a tight tetramer with three independent stable interfaces, protomer flexibility and partial disorder. The C3 loop is mostly disordered in subunits B and C, the Mycobacterium smegmatis enzyme is the first reported unliganded enzyme structure in which the C3 loop is ordered at least partially
additional information
-
enzyme is composed of 6-8 identical subunits
Crystallization/COMMENTARY
ORGANISM
UNIPROT
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
purified wild-type apo-enzyme and enzyme mutant R303C, high throughput screening by sitting drop method, method optimization, mixing of 0.004 ml of protein solution with 0.004 ml of reservoir solution and equilibration against 0.5 ml of reservoir solution, with a precipitant gradient for the native enzyme of 18-28% w/v PEG 6000, 0.1 M Tris, pH 8.0, and 12.5 mM MgCl2 hexahydrate, and for enzyme mutant R303C, a precipitant gradient of 18-28% w/v PEG 8000, 0.1 M Tris, pH 8.5, and 12.5 mM spermine tetrahydrochloride, X-ray diffraction structure determination and analysis at 2.7 A and 2.6 A resolution, respectively
-
purified enzyme, X-ray diffraction structure determination and analysis at 2.16 A resolution
A0R4I6
purified enzyme, X-ray diffraction structure determination is not possible
-
at a resolution of 2.1 A
-
crystal structure is determined to 2.1 resolution. Hanging drop vapor diffusion method at 18C
Q8ZY28
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
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
enzyme is stable for at least 5 days at 25C, and upon rapid freezing and thawing
682657
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
34462
50
-
at 50C the wild type enzyme shows 79-84% of the activity at 25C
708663
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
34462
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
707497
GENERAL STABILITY
ORGANISM
UNIPROT
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
-
the structure of adenylosuccinate lyase reveals that this protein contains three disulfide bonds that contribute significantly to its stability against thermal and chemical denaturation
Q8ZY28
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
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
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
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain Rosetta 2(DE3)pLysS by nickel affinity chromatography
-
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain Rosetta 2(DE3)pLysS by nickel affinity chromatography, dialysis, cleavage of the His-tag through thrombin, and gel filtration, to homogeneity
-
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
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
-
expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain Rosetta 2(DE3)pLysS
-
expression of N-terminally His-tagged wild-type and mutant enzymes in Escherichia coli strain Rosetta 2(DE3)pLysS
-
into the pET-14b vector for expression in Escherichia coli Rosetta 2DE3pLysS cells
-
normal and mutant enzyme S413P, expression in Escherichia coli
-
phylogenetic analysis
A0R4I6
phylogenetic analysis
-
expression of wild-type and mutant enzymes in Escherichia coli strain DH5alpha
O15918
ENGINEERING
ORGANISM
UNIPROT
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
A219V
-
site-directed mutagenesis, inactive mutant
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
R303C
-
naturally occuring mutation, causing the mild form, Type II, of enzyme deficiency, the mutant shows reduced activity compared to the wild-type enzyme, mutation R303C increases the KM value
R303C
-
naturally occuring type II mutation, observed as a homozygous mutation in two unrelated patients, the mutant shows reduced activity compared to the wild-type enzyme, KM values of R303C enzyme mutant increase 4fold for phosphoribosylsuccinyl-aminoimidazole carboxamide compared to that of wild-type enzyme, for succinyladenosine monophosphate the change is almost negligible, substrate binding of the enzyme is latered compared to the wild-type
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
R426H
-
naturally occuring mutation, causing the severe form, Type I, of enzyme deficiency, the mutant shows reduced activity compared to the wild-type enzyme, mutation R426H reduces the KM value
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
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