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6o9s
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Staphylococcus aureus MecR1 antibiotic-sensor domain in complex with avibactam== | |
| + | <StructureSection load='6o9s' size='340' side='right'caption='[[6o9s]], [[Resolution|resolution]] 1.59Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6o9s]] is a 1 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=6O9S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O9S FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.59Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NXL:(2S,5R)-1-FORMYL-5-[(SULFOOXY)AMINO]PIPERIDINE-2-CARBOXAMIDE'>NXL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6o9s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o9s OCA], [https://pdbe.org/6o9s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o9s RCSB], [https://www.ebi.ac.uk/pdbsum/6o9s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o9s ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MECR_STAAU MECR_STAAU] Penicillin-interactive protein and potential antirepressor. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Methicillin-resistant Staphylococcus aureus (MRSA) infections cause significant mortality and morbidity globally. MRSA resistance to beta-lactam antibiotics is mediated by two divergons that control levels of a beta-lactamase, PC1, and a penicillin-binding protein poorly acylated by beta-lactam antibiotics, PBP2a. Expression of genes encoding these proteins is controlled by two integral membrane proteins, BlaR1 and MecR1, which both have an extracellular beta-lactam-binding sensor domain. Here, we solved the X-ray crystallographic structures of the BlaR1 and MecR1 sensor domains in complex with avibactam, a diazabicyclooctane beta-lactamase inhibitor at 1.6-2.0 A resolution. Additionally, we show that S. aureus SF8300, a clinically relevant strain from the USA300 clone of MRSA, responds to avibactam by up-regulating the expression of the blaZ and pbp2a antibiotic-resistance genes, encoding PC1 and PBP2a, respectively. The BlaR1-avibactam structure of the carbamoyl-enzyme intermediate revealed that avibactam is bound to the active-site serine in two orientations approximately 180 degrees to each other. Although a physiological role of the observed alternative pose remains to be validated, our structural results hint at the presence of a secondary sulfate-binding pocket that could be exploited in the design of future inhibitors of BlaR1/MecR1 sensor domains or the structurally similar class D beta-lactamases. The MecR1-avibactam structure adopted a singular avibactam orientation similar to one of the two states observed in the BlaR1-avibactam structure. Given avibactam up-regulates expression of blaZ and pbp2a antibiotic resistance genes, we suggest further consideration and research is needed to explore what effects administering beta-lactam-avibactam combinations have on treating MRSA infections. | ||
| - | + | Structural analysis of avibactam-mediated activation of the bla and mec divergons in methicillin-resistant Staphylococcus aureus.,Alexander JAN, Radaeva M, King DT, Chambers HF, Cherkasov A, Chatterjee SS, Strynadka NCJ J Biol Chem. 2020 Aug 7;295(32):10870-10884. doi: 10.1074/jbc.RA120.013029. Epub , 2020 Jun 9. PMID:32518158<ref>PMID:32518158</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6o9s" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Staphylococcus aureus]] | ||
| + | [[Category: Alexander JAN]] | ||
| + | [[Category: Strynadka NCJ]] | ||
Current revision
Crystal structure of Staphylococcus aureus MecR1 antibiotic-sensor domain in complex with avibactam
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