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| | <StructureSection load='5kmu' size='340' side='right'caption='[[5kmu]], [[Resolution|resolution]] 1.80Å' scene=''> | | <StructureSection load='5kmu' size='340' side='right'caption='[[5kmu]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5kmu]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KMU OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5KMU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5kmu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KMU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KMU FirstGlance]. <br> |
| - | </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=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5kmt|5kmt]]</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=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span></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=5kmu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kmu OCA], [https://pdbe.org/5kmu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kmu RCSB], [https://www.ebi.ac.uk/pdbsum/5kmu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kmu ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5kmu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kmu OCA], [http://pdbe.org/5kmu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kmu RCSB], [http://www.ebi.ac.uk/pdbsum/5kmu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kmu ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q9L5C8_ECOLX Q9L5C8_ECOLX] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Beta-lactamase]] | + | [[Category: Escherichia coli]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Faham, S]] | + | [[Category: Faham S]] |
| - | [[Category: Kasson, P M]] | + | [[Category: Kasson PM]] |
| - | [[Category: Latallo, M]] | + | [[Category: Latallo M]] |
| - | [[Category: Beta lactamase]]
| + | |
| - | [[Category: Esbl]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
Q9L5C8_ECOLX
Publication Abstract from PubMed
The CTX-M family of beta lactamases mediate broad-spectrum antibiotic resistance and are present in the majority of drug-resistant Gram-negative bacterial infections worldwide. Allosteric mutations that increase catalytic rates of these drug resistance enzymes have been identified in clinical isolates but are challenging to predict prospectively. We have used molecular dynamics simulations to predict allosteric mutants increasing CTX-M9 drug resistance, experimentally testing top mutants using multiple antibiotics. Purified enzymes show an increase in catalytic rate and efficiency, while mutant crystal structures show no detectable changes from wild-type CTX-M9. We hypothesize that increased drug resistance results from changes in the conformational ensemble of an acyl intermediate in hydrolysis. Machine-learning analyses on the three top mutants identify changes to the binding-pocket conformational ensemble by which these allosteric mutations transmit their effect. These findings show how molecular simulation can predict how allosteric mutations alter active-site conformational equilibria to increase catalytic rates and thus resistance against common clinically used antibiotics.
Predicting allosteric mutants that increase activity of a major antibiotic resistance enzyme.,Latallo MJ, Cortina GA, Faham S, Nakamoto RK, Kasson PM Chem Sci. 2017 Sep 1;8(9):6484-6492. doi: 10.1039/c7sc02676e. Epub 2017 Jul 19. PMID:28989673[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Latallo MJ, Cortina GA, Faham S, Nakamoto RK, Kasson PM. Predicting allosteric mutants that increase activity of a major antibiotic resistance enzyme. Chem Sci. 2017 Sep 1;8(9):6484-6492. doi: 10.1039/c7sc02676e. Epub 2017 Jul 19. PMID:28989673 doi:http://dx.doi.org/10.1039/c7sc02676e
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