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| | <StructureSection load='6bt6' size='340' side='right'caption='[[6bt6]], [[Resolution|resolution]] 1.05Å' scene=''> | | <StructureSection load='6bt6' size='340' side='right'caption='[[6bt6]], [[Resolution|resolution]] 1.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6bt6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BT6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BT6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6bt6]] is a 2 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=6BT6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BT6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3GK:N-[3-(2H-TETRAZOL-5-YL)PHENYL]-6-(TRIFLUOROMETHYL)-1H-BENZIMIDAZOLE-4-CARBOXAMIDE'>3GK</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]] 1.05Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3GK:N-[3-(2H-TETRAZOL-5-YL)PHENYL]-6-(TRIFLUOROMETHYL)-1H-BENZIMIDAZOLE-4-CARBOXAMIDE'>3GK</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">blaCTX-M ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=6bt6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bt6 OCA], [https://pdbe.org/6bt6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bt6 RCSB], [https://www.ebi.ac.uk/pdbsum/6bt6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bt6 ProSAT]</span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bt6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bt6 OCA], [http://pdbe.org/6bt6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bt6 RCSB], [http://www.ebi.ac.uk/pdbsum/6bt6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bt6 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q9L5C7_ECOLX Q9L5C7_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: Bacillus coli migula 1895]] | + | [[Category: Escherichia coli]] |
| - | [[Category: Beta-lactamase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chen, Y]] | + | [[Category: Chen Y]] |
| - | [[Category: Pemberton, O A]] | + | [[Category: Pemberton OA]] |
| - | [[Category: Esbl]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Tetrazole]]
| + | |
| Structural highlights
Function
Q9L5C7_ECOLX
Publication Abstract from PubMed
CTX-M is the most prevalent family of extended-spectrum beta-lactamases. We recently developed a tetrazole-derived non-covalent inhibitor of CTX-M-9. Here, we present biochemical and microbiological activity of this inhibitor across a representative panel of serine beta-lactamases and Gram-negative bacteria. The compound displayed significant activity against all major subgroups of CTX-M, including CTX-M-15, while exhibiting some low-level inhibition of other serine beta-lactamases. Complex crystal structures with CTX-M-14 S237A mutant and CTX-M-27 illustrate the binding contribution of specific active site residues on the beta3 strand. In vitro pharmacokinetic studies revealed drug-like properties and positive prospects for further optimization. These studies suggest that tetrazole-based compounds can provide novel chemotypes for future serine beta-lactamase inhibitor discovery.
Antibacterial spectrum of a tetrazole-based reversible inhibitor of serine beta-lactamases.,Pemberton OA, Zhang X, Nichols DA, DeFrees K, Jaishankar P, Bonnet R, Adams J, Shaw LN, Renslo AR, Chen Y Antimicrob Agents Chemother. 2018 May 29. pii: AAC.02563-17. doi:, 10.1128/AAC.02563-17. PMID:29844038[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Pemberton OA, Zhang X, Nichols DA, DeFrees K, Jaishankar P, Bonnet R, Adams J, Shaw LN, Renslo AR, Chen Y. Antibacterial spectrum of a tetrazole-based reversible inhibitor of serine beta-lactamases. Antimicrob Agents Chemother. 2018 May 29. pii: AAC.02563-17. doi:, 10.1128/AAC.02563-17. PMID:29844038 doi:http://dx.doi.org/10.1128/AAC.02563-17
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