8cf3
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of S. aureus BlaR1 sensor domain in complex with cefepime== | |
| + | <StructureSection load='8cf3' size='340' side='right'caption='[[8cf3]], [[Resolution|resolution]] 2.52Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8cf3]] is a 2 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=8CF3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CF3 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]] 2.52Å</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=8cf3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cf3 OCA], [https://pdbe.org/8cf3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cf3 RCSB], [https://www.ebi.ac.uk/pdbsum/8cf3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cf3 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/BLAR_STAAU BLAR_STAAU] BlaR1 is a potential penicillin-binding protein required for induction of beta-lactamase. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Infections by Staphylococcus aureus have been treated historically with beta-lactam antibiotics. However, these antibiotics have become obsolete in methicillin-resistant S. aureus by acquisition of the bla and mec operons. The presence of the beta-lactam antibiotic is detected by the sensor domains of BlaR and/or MecR, and the information is transmitted to the cytoplasm, resulting in derepression of the antibiotic-resistance genes. We hypothesized that inhibition of the sensor domain would shut down this response system, and beta-lactam susceptibility would be restored. An in silico search of 11 million compounds led to a benzimidazole-based hit and, ultimately, to the boronate 4. The X-ray structure of 4 is covalently engaged with the active-site serine of BlaR. Compound 4 potentiates by 16- to 4,096-fold the activities of oxacillin and of meropenem against methicillin-resistant S. aureus strains. The combination of 4 with oxacillin or meropenem shows efficacy in infected mice, validating the strategy. | ||
| - | + | Restoring susceptibility to beta-lactam antibiotics in methicillin-resistant Staphylococcus aureus.,Nguyen VT, Birhanu BT, Miguel-Ruano V, Kim C, Batuecas M, Yang J, El-Araby AM, Jimenez-Faraco E, Schroeder VA, Alba A, Rana N, Sader S, Thomas CA, Feltzer R, Lee M, Fisher JF, Hermoso JA, Chang M, Mobashery S Nat Chem Biol. 2024 Jul 26. doi: 10.1038/s41589-024-01688-0. PMID:39060390<ref>PMID:39060390</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 8cf3" style="background-color:#fffaf0;"></div> |
| - | [[Category: Hermoso | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Staphylococcus aureus]] | ||
| + | [[Category: Hermoso JA]] | ||
| + | [[Category: Miguel-Ruano V]] | ||
Current revision
Crystal structure of S. aureus BlaR1 sensor domain in complex with cefepime
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