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Information on EC 6.3.2.6 - phosphoribosylaminoimidazolesuccinocarboxamide synthase and Organism(s) Homo sapiens

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EC Tree
IUBMB Comments
Forms part of the purine biosynthesis pathway.
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This record set is specific for:
Homo sapiens
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The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
saicar synthetase, saicar synthase, phosphoribosylaminoimidazole succinocarboxamide synthetase, airc-saicars, phosphoribosylaminoimidazole-succinocarboxamide synthase, phosphoribosylaminoimidazolesuccinocarboxamide synthetase, sppurc, bapurc, phosphoribosylaminoimidazolesuccinocarboxamide synthase, phosphoribosylaminoimidazole-succinocarboxamide synthetase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5-Aminoimidazole-4-N-succinocarboxamide ribonucleotide synthetase
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N-(5-Amino-1-ribosyl-4-imidazolylcarbonyl)-L-aspartic acid 5´-phosphate synthetase
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PAICS
phosphoribosylaminoimidazole succinocarboxamide synthetase
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bifunctional enzyme with both 5-aminoimidazole ribonucleotide carboxylase (AIRc) and 4-(N-succinylcarboxamide)-5-aminoimidazole ribonucleotide synthetase (SAICARs) activities
Phosphoribosylaminoimidazolesuccinocarboxamide synthetase
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PurCE
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SAICAR synthase
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SAICAR synthetase
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Succino-AICAR synthetase
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Synthetase, phosphoribosylaminoimidazolesuccinocarboxamide
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VEG286A
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Vegetative protein 286A
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additional information
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the enzyme is a member of the ATP-grasp superfamily
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
carboxamide formation
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carboxylic acid amide formation
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate:L-aspartate ligase (ADP-forming)
Forms part of the purine biosynthesis pathway.
CAS REGISTRY NUMBER
COMMENTARY hide
9023-67-0
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + L-aspartate
ADP + phosphate + (S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
show the reaction diagram
additional information
?
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in higher organisms PurC and PurE are fused to form a bifunctional enzyme, overview, active site structure, overview
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate + L-aspartate
ADP + phosphate + (S)-2-[5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido]succinate
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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Manually annotated by BRENDA team
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quantitative real-time RT-PCR measurement of purine biosynthesis metabolism enzymes PPAT, PAICS, PKM2 and PKM1 transcripts in lung adenocarcinomas, overview
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
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increased expression of the enzymes of de novo purine biosynthetic pathway in lung adenocarcinomas, phosphoribosyl amidotransferase (PPAT), phosphoribosylaminoimidazole carboxylase, and phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS). Modulation of PPAT and PAICS or glutamine treatment alters pyruvate kinase (PK) activity, overview
physiological function
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enzyme phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) produces the intermediary metabolite N-succinyl-5-aminoimidazole-4-carboxamide-1-ribose-5'-phosphate (SAICAR), known to activate pyruvate kinase isoform PKM2 under glucose-depleted condi­tion. Increased expression of the enzymes of de novo purine biosynthetic pathway in lung adenocarcinomas, phosphoribosyl amidotransferase (PPAT), phosphoribosylaminoimidazole carboxylase, and PAICS. PAICS shows increased expression with disease progression and is significantly associated with poor prognosis. Altering PPAT and PAICS expression modulates pyruvate kinase activity, cell proliferation and invasion. Regulation of both PPAT and PAICS and pyruvate kinase activity by L-glutamine, a co-substrate for PPAT. PPAT and PAICS genes are necessary for lung tumorigenesis
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PUR6_HUMAN
425
0
47079
Swiss-Prot
other Location (Reliability: 1)
B4DGX3_HUMAN
280
0
31555
TrEMBL
other Location (Reliability: 1)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
octamer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
the 2.8 A resolution structure reveals that eight PAICS subunits, each composed of distinct AIRc and SAICARs domains, assemble a compact homo-octamer with an octameric-carboxylase core and four symmetric periphery dimers formed by synthetase domains
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene PAICS, quantitative real-time RT-PCR enzyme expression analysis
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
regulation of both phosphoribosyl amidotransferase (PPAT) and phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), and of pyruvate kinase activity, by L-glutamine, a co-substrate for PPAT. A glutamine antagonist, 6-diazo-5-oxo-L-norleucine (DON) blocks glutamine mediated induction of PPAT and PAICS as well as reduced pyruvate kinase activity, which is completely reversible by addition of L-glutamate
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) is an important bifunctional enzyme in de novo purine biosynthesis in vertebrate with both 5-aminoimidazole ribonucleotide carboxylase (AIRc) and 4-(N-succinylcarboxamide)-5-aminoimidazole ribonucleotide synthetase (SAICARs) activities. It is an attractive target for rational anticancer drug design, since rapidly dividing cancer cells rely heavily on the purine de novo pathway for synthesis of adenine and guanine, whereas normal cells favor the salvage pathway
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Li, S.; Tong, Y.; Xie, X.; Wang, Q.; Zhou, H.; Han, Y.; Zhang, Z.; Gao, W.; Li, S.; Zhang, X.C.; Bi, R.
Octameric structure of the human bifunctional enzyme PAICS in purine biosynthesis
J. Mol. Biol.
366
1603-1614
2007
Homo sapiens
Manually annotated by BRENDA team
Zhang, Y.; Morar, M.; Ealick, S.E.
Structural biology of the purine biosynthetic pathway
Cell. Mol. Life Sci.
65
3699-3724
2008
Escherichia coli, Homo sapiens, Thermotoga maritima, Saccharomyces cerevisiae (P27616)
Manually annotated by BRENDA team
Goswami, M.T.; Chen, G.; Chakravarthi, B.V.; Pathi, S.S.; Anand, S.K.; Carskadon, S.L.; Giordano, T.J.; Chinnaiyan, A.M.; Thomas, D.G.; Palanisamy, N.; Beer, D.G.; Varambally, S.
Role and regulation of coordinately expressed de novo purine biosynthetic enzymes PPAT and PAICS in lung cancer
Oncotarget
6
23445-23461
2015
Homo sapiens
Manually annotated by BRENDA team