Structural highlights
4hus 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: | CL, EDO, NA, PEG, PGE, SO4, VIR |
| Related: | 4hur, 4e8l |
| Gene: | vat ("Micrococcus aureus" (Rosenbach 1884) Zopf 1885) |
| 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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Stogios PJ, Kuhn ML, Evdokimova E, Courvalin P, Anderson WF, Savchenko A. Potential for reduction of streptogramin A resistance revealed by structural analysis of the VatA acetyltransferase. Antimicrob Agents Chemother. 2014 Sep 15. pii: AAC.03743-14. PMID:25223995 doi:https://dx.doi.org/10.1128/AAC.03743-14
