4hur | pdb_00004hur

Crystal structure of streptogramin group A antibiotic acetyltransferase VatA from Staphylococcus aureus in complex with acetyl coenzyme A

spinqualitylabelsall models 4hur, resolution 2.15Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hur is a 3 chain structure with sequence from "micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACO, CL, EDO, NA, SO4 Related: 4hus, 4e8l Gene: vat ("Micrococcus aureus" (Rosenbach 1884) Zopf 1885) Resources: FirstGlance, OCA, RCSB, PDBsum Function [VATA_STAAU] Inactivates the A compounds of virginiamycin-like antibiotics, thus providing resistance to these antibiotics. Publication Abstract from PubMed Combinations of streptogramins of group A and B (i.e. dalfoprisin and quinipristin) are "last-resort" antibiotics for treatment of infections caused by Gram-positive pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Resistance to streptogramins has arisen via multiple mechanisms, including deactivation of the group A component by the large family of virginamycin O-acetyltransferase (Vat) enzymes. Despite the structural elucidation performed for the VatD acetyltransferase which provided a general molecular framework for activity, detailed characterization of the essential catalytic and antibiotic substrate-binding determinants in Vat enzymes is still lacking. We have determined the crystal structure of S. aureus VatA in apo, virginiamycin M1- and acetyl CoA-bound forms and provide an extensive mutagenesis and functional analysis of the structural determinants required for catalysis and streptogramin A recognition. Based on an updated genomic survey across the Vat enzyme family we identified key conserved residues critical for VatA activity that are not part of the O-acetylation catalytic apparatus. Exploiting such constraints of the Vat active site may lead to development of streptogramin A compounds that evade inactivation by Vat enzymes while retaining binding to their ribosomal target. Potential for reduction of streptogramin A resistance revealed by structural analysis of the VatA acetyltransferase.,Stogios PJ, Kuhn ML, Evdokimova E, Courvalin P, Anderson WF, Savchenko A Antimicrob Agents Chemother. 2014 Sep 15. pii: AAC.03743-14. PMID:25223995 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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