3orq | pdb_00003orq

Crystal Structure of N5-Carboxyaminoimidazole synthetase from Staphylococcus aureus complexed with ADP

spinqualitylabelsall models 3orq, resolution 2.23Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3orq is a 2 chain structure with sequence from Staphylococcus aureus subsp. aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ADP, GOL, MG, POP NonStd Res: MSE Related: 3orr, 3ors Gene: NWMN_0934, purK (Staphylococcus aureus subsp. aureus) Activity: 5-(carboxyamino)imidazole ribonucleotide synthase, with EC number 6.3.4.18 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed With the rapid rise of methicillin-resistant Staphylococcus aureus infections, new strategies against S. aureus are urgently needed. De novo purine biosynthesis is a promising yet unexploited target, insofar as abundant evidence has shown that bacteria with compromised purine biosynthesis are attenuated. Fundamental differences exist within the process by which humans and bacteria convert 5-aminoimidazole ribonucleotide (AIR) to 4-carboxy-5-aminoimidazole ribonucleotide (CAIR). In bacteria, this transformation occurs through a two-step conversion catalyzed by PurK and PurE; in humans, it is mediated by a one-step conversion catalyzed by class II PurE. Thus, these bacterial enzymes are potential targets for selective antibiotic development. Here, the first comprehensive structural and biochemical characterization of PurK and PurE from S. aureus is presented. Structural analysis of S. aureus PurK reveals a nonconserved phenylalanine near the AIR-binding site that occupies the putative position of the imidazole ring of AIR. Mutation of this phenylalanine to isoleucine or tryptophan reduced the enzyme efficiency by around tenfold. The K(m) for bicarbonate was determined for the first time for a PurK enzyme and was found to be approximately 18.8 mM. The structure of PurE is described in comparison to that of human class II PurE. It is confirmed biochemically that His38 is essential for function. These studies aim to provide foundations for future structure-based drug-discovery efforts against S. aureus purine biosynthesis. Structural and biochemical characterization of N5-carboxyaminoimidazole ribonucleotide synthetase and N5-carboxyaminoimidazole ribonucleotide mutase from Staphylococcus aureus.,Brugarolas P, Duguid EM, Zhang W, Poor CB, He C Acta Crystallogr D Biol Crystallogr. 2011 Aug;67(Pt 8):707-15. Epub 2011 Jul 12. PMID:21795812 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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