4hus: Difference between revisions
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==Crystal structure of streptogramin group A antibiotic acetyltransferase VatA from Staphylococcus aureus in complex with virginiamycin M1== | ==Crystal structure of streptogramin group A antibiotic acetyltransferase VatA from Staphylococcus aureus in complex with virginiamycin M1== | ||
<StructureSection load='4hus' size='340' side='right' caption='[[4hus]], [[Resolution|resolution]] 2.36Å' scene=''> | <StructureSection load='4hus' size='340' side='right'caption='[[4hus]], [[Resolution|resolution]] 2.36Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4hus]] is a 3 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4hus]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HUS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HUS FirstGlance]. <br> | ||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VIR:VIRGINIAMYCIN+M1'>VIR</scene> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.36Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VIR:VIRGINIAMYCIN+M1'>VIR</scene></td></tr> | |||
<tr | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4hus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hus OCA], [https://pdbe.org/4hus PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hus RCSB], [https://www.ebi.ac.uk/pdbsum/4hus PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hus ProSAT]</span></td></tr> | ||
</table> | |||
<table> | == Function == | ||
[https://www.uniprot.org/uniprot/VATA_STAAU VATA_STAAU] Inactivates the A compounds of virginiamycin-like antibiotics, thus providing resistance to these antibiotics. | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 16: | Line 18: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4hus" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Staphylococcus aureus]] | ||
[[Category: Courvalin | [[Category: Anderson WF]] | ||
[[Category: | [[Category: Courvalin P]] | ||
[[Category: | [[Category: Di Leo R]] | ||
[[Category: | [[Category: Evdokimova E]] | ||
[[Category: Minasov | [[Category: Krishnamoorthy M]] | ||
[[Category: Savchenko | [[Category: Minasov G]] | ||
[[Category: Stogios | [[Category: Savchenko A]] | ||
[[Category: Wawrzak | [[Category: Stogios PJ]] | ||
[[Category: Yim | [[Category: Wawrzak Z]] | ||
[[Category: Yim V]] | |||
Latest revision as of 18:11, 20 September 2023
Crystal structure of streptogramin group A antibiotic acetyltransferase VatA from Staphylococcus aureus in complex with virginiamycin M1Crystal structure of streptogramin group A antibiotic acetyltransferase VatA from Staphylococcus aureus in complex with virginiamycin M1
Structural highlights
FunctionVATA_STAAU Inactivates the A compounds of virginiamycin-like antibiotics, thus providing resistance to these antibiotics. Publication Abstract from PubMedCombinations 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
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