Information on EC 6.3.4.4 - Adenylosuccinate synthase

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

EC NUMBER
COMMENTARY hide
6.3.4.4
-
RECOMMENDED NAME
GeneOntology No.
Adenylosuccinate synthase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
GTP + IMP + L-aspartate = GDP + phosphate + N6-(1,2-dicarboxyethyl)-AMP
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
amination
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
adenosine ribonucleotides de novo biosynthesis
-
-
Alanine, aspartate and glutamate metabolism
-
-
Metabolic pathways
-
-
purine metabolism
-
-
Purine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
IMP:L-aspartate ligase (GDP-forming)
-
CAS REGISTRY NUMBER
COMMENTARY hide
9023-57-8
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain pabaA1
-
-
Manually annotated by BRENDA team
strain pabaA1
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Cryptococcus neoformans variant grubii
-
-
Manually annotated by BRENDA team
Cryptococcus neoformans variant grubii
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
ADSS1 inactivation as a somatic alteration causing lung carcinogenesis
metabolism
physiological function
-
genetic variation of inosine triphosphatase causing an accumulation of inosine triphosphate protects patients against ribavirin-induced anemia during treatment for chronic hepatitis C infection. ITP can be used for ATP biosynthesis via adenylosuccinate synthase in place of guanosine triphosphate. With ribavirin challenge, erythrocyte ATP reduction is more severe in the wild-type inosine triphosphatase ITPA genotype than in the hemolysis protective ITPA genotype. The alleviation of ATP reduction by the hemolysis protective ITPA genotype is canceled by the adenylosuccinate synthase inhibitor 6-mercaptoethanol
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2'-dGTP + IMP + L-aspartate
2'-dGDP + phosphate + adenylosuccinate
show the reaction diagram
-
-
-
?
ATP + IMP + L-Asp
GDP + phosphate + adenylosuccinate
show the reaction diagram
ddGTP + IMP + L-aspartate
ddGDP + phosphate + adenylosuccinate
show the reaction diagram
-
-
-
?
GTP + 2'-dIMP + L-Asp
GDP + phosphate + 2'-deoxysuccinoAMP
show the reaction diagram
GTP + 4-hydroxypyrazolo[3,4-d]pyrimidine ribonucleotide + L-Asp
GDP + phosphate + 4-aminopyrazolo[3,4-d]pyrimidine ribonucleotide
show the reaction diagram
GTP + 8-azaIMP + L-Asp
GDP + phosphate + 8-azasuccinoAMP
show the reaction diagram
GTP + beta-D-arabinosylIMP + L-Asp
GDP + phosphate + arabinosylsuccinoAMP
show the reaction diagram
GTP + IMP + 6-methoxypurine nucleotide
?
show the reaction diagram
-
-
-
-
-
GTP + IMP + Ala-3-nitronate
GDP + phosphate + N6-(L-1-carboxy-2-nitroethyl)AMP
show the reaction diagram
-
-
-
-
GTP + IMP + cysteine sulfinate
?
show the reaction diagram
-
-
-
-
-
GTP + IMP + hydroxylamine
GDP + phosphate + ?
show the reaction diagram
-
-
-
?
GTP + IMP + L-Asp
?
show the reaction diagram
GTP + IMP + L-Asp
GDP + phosphate + adenylosuccinate
show the reaction diagram
GTP + IMP + L-aspartate
GDP + phosphate + adenosylsuccinate
show the reaction diagram
GTP + IMP + L-aspartate
GDP + phosphate + adenylosuccinate
show the reaction diagram
GTP + IMP + L-aspartate
GDP + phosphate + N6-(1,2-dicarboxyethyl)-AMP
show the reaction diagram
GTP + ITP + L-aspartate
?
show the reaction diagram
-
-
-
?
ITP + IMP + L-Asp
IDP + phosphate + adenylosuccinate
show the reaction diagram
ITP + IMP + L-aspartate
IDP + phosphate + adenylosuccinate
show the reaction diagram
-
-
-
?
UTP + IMP + L-Asp
UDP + phosphate + adenylosuccinate
show the reaction diagram
-
-
-
-
XTP + IMP + L-Asp
XDP + phosphate + adenylosuccinate
show the reaction diagram
-
-
-
-
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
GTP + IMP + L-Asp
?
show the reaction diagram
GTP + IMP + L-Asp
GDP + phosphate + adenylosuccinate
show the reaction diagram
GTP + IMP + L-aspartate
GDP + phosphate + adenosylsuccinate
show the reaction diagram
-
function in adenine nucleotide biosynthesis
-
?
GTP + IMP + L-aspartate
GDP + phosphate + adenylosuccinate
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ni2+
-
can replace Mg2+ with lower efficiency
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(+)-Hydantocidin
-
-
(NH4)2SO4
-
25 mM
2,4-dihydro-4-(beta-D-ribofuranosyl)-1,2,4(3H)-triazol-3-one
2-mercaptosuccinate
-
-
3',5'-cyclic GMP
4-Oxo-2-aminopentanoic acid
-
i.e. 2-oxonorvaline, poor
5,5'-dithiobis(2-nitrobenzoate)
-
-
5-amino-4-(N-succinocarboxamide)imidazole ribonucleotide
-
-
5-amino-4-carbamoyl-imidazole ribonucleotide
-
-
6-(4-bromo-2,3-dioxobutyl)thioadenosine 5'-monophosphate
-
-
6-mercaptopurine ribonucleotide
-
-
6-mercaptopurine riboside 5'-phosphate
-
-
6-Thio-GMP
6-thio-IMP
-
-
8-Aza-7-deaza-GMP
8-aza-GMP
8-Aza-IMP
-
-
acyclo-GMP
-
-
adenosine 3',5'-AMP
-
-
adenylosuccinate
allopurinol nucleotide
-
-
arabinosyl-GMP
argininosuccinate
aspartate analogs
-
-
beta,gamma-5'-Guanylylmethylene diphosphate
-
-
Ca2+
-
in presence of Mg2+
Carbamoylphosphate
-
-
Cd2+
-
in presence of Mg2+
CDP
-
-
CMP
-
-
cyanoalanine
-
poor
cyclic GMP
-
-
cysteine
-
poor
cysteine sulfonate
-
poor
D-fructose 1,6 bisphosphate
competitive with IMP and noncompetitive against GTP
D-fructose 1,6-bisphosphate
-
inhibits both isozymes competitively
dAMP
-
-
dCMP
-
-
dGDP
-
-
Formycin B monophosphate
-
-
fructose 1,6-diphosphate
fumarate
guanosine
-
-
guanosine 5'-(beta,gamma-imino)triphosphate
-
-
guanosine 5'-diphosphate
-
-
Guanosine 5'-diphosphate-3'-diphosphate
-
competitive with respect to GTP and noncompetitive with respect to L-Asp and IMP
Guanosine 5'-O-[S-(4-bromo-2,3-dioxobutyl)thio]phosphate
-
-
Hadacidin
Hg2+
-
reversed by addition of DTT
homocysteine
-
poor
Hydantocidin 5'-phosphate
hydroxylamine
-
-
Maleate
methionine sulfone
-
poor
Mn2+
-
in presence of Mg2+
N-(Thiocarboxy)-L-aspartic anhydride
-
5 mM, 27.5% inhibition
N-Acetyl-5'-phosphohydantocidin
N-Acetyl-N-hydroxyglycine
-
5 mM, 72.9% inhibition
N-acetylglycine
-
5 mM, 51.2% inhibition
N-benzoylglycine
-
5 mM, 6% inhibition
N-formyl-N-hydroxyglycine
i.e. hadacidin. competitive inhibitor of aspartate, showed uncompetitive inhibition with IMP and GTP
-
N-Formylglycine
-
5 mM, 61.1% inhibition
N-Hydroxyaspartate
-
poor
N-Hydroxyglycine
-
5 mM, 49.3% inhibition
N-methylaspartate
-
poor
nucleotides
-
acidic type L isozyme more strongly inhibited than basic type M isozyme
-
oligonucleotides
-
inhibition by single-stranded autonomously replicating sequences, highly specific inhibition by a 44-base DNA oligonucleotide carrying the autonomously replicating sequences core consensus sequence
oxaloacetate
-
-
Pb2+
-
in presence of Mg2+
Phenylglyoxal
-
GTP or IMP partially protect
phosphate
phosphoenolpyruvate
-
-
SCN-
-
i.e. thiocyanate
succinate
TDP
-
-
TMP
-
-
UDP
-
-
UMP
-
-
Zn2+
-
in presence of Mg2+
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
AMP
-
ASS expression is induced by AMP
D-fructose 1,6 bisphosphate
-
binds to the Asp loop and induces a conformation that facilitates aspartate binding to the enzyme active site
D-fructose 1,6-diphosphate
-
activates
NH4+
-
ASS expression is induced rather than repressed by NH4
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.041 - 0.48
2'-dIMP
0.05
8-azaIMP
-
-
0.34
allopurinol ribonucleotide
0.26
arabinosylIMP
0.03 - 5.4
Asp
0.17 - 2.6
aspartate
0.85
beta-D-arabinosylIMP
-
-
0.004 - 1.7
GTP
91 - 255
hydroxylamine
0.009 - 3.8
IMP
1.07 - 17.3
ITP
0.004 - 3.3
L-Asp
0.01 - 9
L-aspartate
1.27 - 4.38
UTP
0.0286 - 0.388
XTP
additional information
additional information
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.96 - 5.5
2'-dIMP
0.0048 - 6.08
GTP
0.08 - 0.5
hydroxylamine
0.0038 - 4.2
IMP
0.96 - 5.5
L-Asp
0.45 - 4.2
L-aspartate
additional information
additional information
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0406
6-(4-bromo-2,3-dioxobutyl)thioadenosine 5'-monophosphate
-
pH 7.0, 25C
0.0094 - 2.7
adenylosuccinate
0.0582 - 6
AMP
4
ATP
-
pH 8.0, 25C
8
Cl-
-
pH 8.0, 25C
1.5 - 4.8
D-fructose 1,6 bisphosphate
0.016 - 0.67
D-fructose 1,6-bisphosphate
0.04 - 0.64
fumarate
0.0053 - 0.0822
GDP
0.012 - 0.12
GMP
0.00032 - 0.017
Hadacidin
0.078 - 3.1
Maleate
0.0105 - 0.0269
N-formyl-N-hydroxyglycine
1.9 - 28
phosphate
0.08 - 1
succinate