9qi3
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of I105Y/S130G double mutant of BlaC from Mycobacterium tuberculosis== | |
| + | <StructureSection load='9qi3' size='340' side='right'caption='[[9qi3]], [[Resolution|resolution]] 1.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9qi3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9QI3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9QI3 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]] 1.3Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=9qi3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9qi3 OCA], [https://pdbe.org/9qi3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9qi3 RCSB], [https://www.ebi.ac.uk/pdbsum/9qi3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9qi3 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/BLAC_MYCBO BLAC_MYCBO] Extended spectrum beta-lactamase (ESBL) that inactivates beta-lactam antibiotics by hydrolyzing the amide group of the beta-lactam ring. Displays high levels of penicillinase and cephalosporinase activity as well as measurable activity with carbapenems, including imipenem and meropenem. Plays a primary role in the intrinsic resistance of mycobacteria to beta-lactam antibiotics.[UniProtKB:P9WKD3] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Epistasis, the non-additive effect of mutations, substantially undermines our ability to predict the evolutionary trajectories of enzymes. Epistatic effects are evident in the evolution of serine beta-lactamases, where synergistic mutations can enhance antimicrobial resistance. We recently demonstrated that positive epistasis drives clavulanic acid resistance in double-mutant libraries of the beta-lactamase BlaC. Here, we employed various biochemical and structural approaches to investigate molecular mechanisms underlying epistasis in the fitness of two double mutant variants, I105Y-S130G and I105G-G132N. For the latter enzyme, epistatic compensation of catalytic activity was detected for multiple substrates and proved to be highly buffer-dependent. Non-additive effects were also evident in the thermostability profile of the I105G-G132N variant. The interplay between the reduced clavulanic acid sensitivity of the S130G and G132N variants and active-site modifications induced by Ile105 substitutions is discussed. The results demonstrate that the origins of epistasis can be rooted in multiple enzyme traits, highlighting its important role in the evolution of antimicrobial resistance. | ||
| - | + | Phosphate ions modulate enzyme activity and epistatic effects in two clavulanic acid-resistant beta-lactamase mutants.,Radojkovic M, Koene SF, Chikunova A, Florea BI, Natarajan SV, Boyle AL, Ubbink M Protein Sci. 2025 Nov;34(11):e70325. doi: 10.1002/pro.70325. PMID:41074856<ref>PMID:41074856</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Chikunova | + | <div class="pdbe-citations 9qi3" style="background-color:#fffaf0;"></div> |
| - | [[Category: Radojkovic | + | == References == |
| - | [[Category: Ubbink | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mycobacterium tuberculosis]] | ||
| + | [[Category: Chikunova A]] | ||
| + | [[Category: Radojkovic M]] | ||
| + | [[Category: Ubbink M]] | ||
Current revision
Crystal structure of I105Y/S130G double mutant of BlaC from Mycobacterium tuberculosis
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