4hus

Crystal structure of streptogramin group A antibiotic acetyltransferase VatA from Staphylococcus aureus in complex with virginiamycin M1

spinqualitylabelsall models 4hus, resolution 2.36Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4hus is a 3 chain structure with sequence from Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.36Å Ligands: CL, EDO, NA, PEG, PGE, SO4, VIR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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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