2gqs
SAICAR Synthetase Complexed with CAIR-Mg2+ and ADP
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OverviewOverview
Phosphoribosylaminoimidazole-succinocarboxamide synthetase (SAICAR, synthetase) converts 4-carboxy-5-aminoimidazole ribonucleotide (CAIR) to, 4-(N-succinylcarboxamide)-5-aminoimidazole ribonucleotide (SAICAR). The, enzyme is a target of natural products that impair cell growth. Reported, here are the crystal structures of the ADP and the ADP.CAIR complexes of, SAICAR synthetase from Escherichia coli, the latter being the first, instance of a CAIR-ligated SAICAR synthetase. ADP and CAIR bind to the, active site in association with three Mg(2+), two of which coordinate the, same oxygen atom of the 4-carboxyl group of CAIR; whereas, the third, coordinates the alpha- and beta-phosphoryl groups of ADP. The ADP.CAIR, complex is the basis for a transition state model of a phosphoryl transfer, reaction involving CAIR and ATP, but also supports an alternative chemical, pathway in which the nucleophilic attack of l-aspartate precedes the, phosphoryl transfer reaction. The polypeptide fold for residues 204-221 of, the E. coli structure differs significantly from those of the ligand-free, SAICAR synthetase from Thermatoga maritima and the adenine nucleotide, complexes of the synthetase from Saccharomyces cerevisiae. Conformational, differences between the E. coli, T. maritima, and yeast synthetases, suggest the possibility of selective inhibition of de novo purine, nucleotide biosynthesis in microbial organisms.
About this StructureAbout this Structure
2GQS is a Single protein structure of sequence from Escherichia coli with MG, ADP, C2R and FMT as ligands. Active as Phosphoribosylaminoimidazolesuccinocarboxamide synthase, with EC number 6.3.2.6 Full crystallographic information is available from OCA.
ReferenceReference
Nucleotide complexes of Escherichia coli phosphoribosylaminoimidazole succinocarboxamide synthetase., Ginder ND, Binkowski DJ, Fromm HJ, Honzatko RB, J Biol Chem. 2006 Jul 28;281(30):20680-8. Epub 2006 May 9. PMID:16687397
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