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9hck
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 9hck is ON HOLD Authors: Sun, J., Bruenle, S., Ubbink, M. Description: Structure of P167S/D240G/D172A/S104G BlaC from Mycobacterium tuberculosis at...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of P167S/D240G/D172A/S104G BlaC from Mycobacterium tuberculosis at pH 5.5== | |
| + | <StructureSection load='9hck' size='340' side='right'caption='[[9hck]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9hck]] is a 1 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=9HCK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9HCK 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]] 1.6Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH4:AMMONIUM+ION'>NH4</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=9hck FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9hck OCA], [https://pdbe.org/9hck PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9hck RCSB], [https://www.ebi.ac.uk/pdbsum/9hck PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9hck ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/BLAC_MYCTU BLAC_MYCTU] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | In directed evolution, enzyme activity is improved in successive generations of laboratory evolution, which can be described by a simple stepwise climb toward a peak in the fitness landscape. In a naive model of evolution, it can be assumed that each enzyme variant along this path is in a single, well-defined state that differs slightly from the previous one. We analyzed the structural changes in mutants of the beta-lactamase BlaC from Mycobacterium tuberculosis obtained via directed evolution for increased ceftazidime hydrolysis activity. Crystal structures of three successive mutants only show an increase in the dynamics of a loop that lines the active site (Omega-loop), enabling better access of the large substrate. However, NMR spectra of wild type and nine mutants of different branches of the directed evolution experiment show a much more diverse and complex picture of the conformational effects. Many mutants show micro-millisecond dynamics for certain regions and most show peak doubling, indicative of two or more conformations being populated. Thus, the straightforward climb to increased ceftazidime activity in the fitness landscape masks a complex trajectory in the conformational landscape, emphasizing the complex and epistatic interplay that single mutations can have on the structure and dynamics of enzymes. | ||
| - | + | Directed evolution of a beta-lactamase samples a wide variety of conformational states.,Sun J, Timmer M, Brunle S, Boyle AL, Ubbink M Protein Sci. 2025 Nov;34(11):e70322. doi: 10.1002/pro.70322. PMID:41074874<ref>PMID:41074874</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 9hck" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mycobacterium tuberculosis]] | ||
| + | [[Category: Bruenle S]] | ||
| + | [[Category: Sun J]] | ||
| + | [[Category: Ubbink M]] | ||
Current revision
Structure of P167S/D240G/D172A/S104G BlaC from Mycobacterium tuberculosis at pH 5.5
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