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Literature summary for 4.3.2.2 extracted from

  • Ray, S.P.; Duval, N.; Wilkinson, T.G.; Shaheen, S.E.; Ghosh, K.; Patterson, D.
    Inherent properties of adenylosuccinate lyase could explain S-Ado/SAICAr ratio due to homozygous R426H and R303C mutations (2013), Biochim. Biophys. Acta, 1834, 1545-1553.
    View publication on PubMed
Search for more literature for 4.3.2.2

Cloned(Commentary)

Cloned (Comment) Organism
expression of N-terminally His-tagged wild-type and mutant enzymes in Escherichia coli strain Rosetta 2(DE3)pLysS Homo sapiens

Protein Variants

Protein Variants Comment Organism
A219V site-directed mutagenesis, inactive mutant Homo sapiens
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 Homo sapiens
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 Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
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 Homo sapiens
0.0007
-
 phosphoribosylsuccinyl-aminoimidazole carboxamide recombinant His-tagged mutant R426H, pH 7.4, 25°C Homo sapiens
0.0014
-
 succinyladenosine monophosphate recombinant His-tagged mutant R426H, pH 7.4, 25°C Homo sapiens
0.00174
-
 phosphoribosylsuccinyl-aminoimidazole carboxamide recombinant His-tagged wild-type enzyme, pH 7.4, 25°C Homo sapiens
0.0021
-
 succinyladenosine monophosphate recombinant His-tagged wild-type enzyme, pH 7.4, 25°C Homo sapiens
0.0027
-
 succinyladenosine monophosphate recombinant His-tagged mutant R303C, pH 7.4, 25°C Homo sapiens
0.009
-
 phosphoribosylsuccinyl-aminoimidazole carboxamide recombinant His-tagged mutant R303C, pH 7.4, 25°C Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
phosphoribosylsuccinyl-aminoimidazole carboxamide Homo sapiens
-
 phosphoribosylaminoimidazole carboxamide + fumarate
-
 ?
succinyladenosine monophosphate Homo sapiens
-
 AMP + fumarate
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain Rosetta 2(DE3)pLysS by nickel affinity chromatography Homo sapiens

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
6.4
-
 purified recombinant His-tagged mutant R426H enzyme, substrate phosphoribosylsuccinyl-aminoimidazole carboxamide, pH 7.4, 25°C Homo sapiens
6.7
-
 purified recombinant His-tagged mutant R426H enzyme, substrate succinyladenosine monophosphate, pH 7.4, 25°C Homo sapiens
13.9
-
 purified recombinant His-tagged wild-type enzyme, substrate succinyladenosine monophosphate, pH 7.4, 25°C Homo sapiens
23.3
-
 purified recombinant His-tagged wild-type enzyme, substrate phosphoribosylsuccinyl-aminoimidazole carboxamide, pH 7.4, 25°C Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
phosphoribosylsuccinyl-aminoimidazole carboxamide
-
 Homo sapiens phosphoribosylaminoimidazole carboxamide + fumarate
-
 ?
succinyladenosine monophosphate
-
 Homo sapiens AMP + fumarate
-
 ?

Subunits

Subunits Comment Organism
homotetramer
-
 Homo sapiens

Synonyms

Synonyms Comment Organism
ADSL
-
 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
 assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.4
-
 assay at Homo sapiens

General Information

General Information Comment Organism
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 Homo sapiens
metabolism adenylosuccinate lyase is involved in the de novo purine biosynthesis pathway and purine nucleotide cycle Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
915
-
 succinyladenosine monophosphate recombinant His-tagged mutant R303C, pH 7.4, 25°C Homo sapiens
3640
-
 phosphoribosylsuccinyl-aminoimidazole carboxamide recombinant His-tagged mutant R303C, pH 7.4, 25°C Homo sapiens
17800
-
 succinyladenosine monophosphate recombinant His-tagged mutant R426H, pH 7.4, 25°C Homo sapiens
25200
-
 succinyladenosine monophosphate recombinant His-tagged wild-type enzyme, pH 7.4, 25°C Homo sapiens
37500
-
 phosphoribosylsuccinyl-aminoimidazole carboxamide recombinant His-tagged mutant R426H, pH 7.4, 25°C Homo sapiens
50900
-
 phosphoribosylsuccinyl-aminoimidazole carboxamide recombinant His-tagged wild-type enzyme, pH 7.4, 25°C Homo sapiens