4de0: Difference between revisions
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==CTX-M-9 class A beta-lactamase complexed with compound 16== | ==CTX-M-9 class A beta-lactamase complexed with compound 16== | ||
<StructureSection load='4de0' size='340' side='right' caption='[[4de0]], [[Resolution|resolution]] 1.12Å' scene=''> | <StructureSection load='4de0' size='340' side='right'caption='[[4de0]], [[Resolution|resolution]] 1.12Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4de0]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4de0]] 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=4DE0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DE0 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.12Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0JB:N-[3-(1H-TETRAZOL-5-YL)PHENYL]-1H-BENZIMIDAZOLE-7-CARBOXAMIDE'>0JB</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> | |||
<tr id=' | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4de0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4de0 OCA], [https://pdbe.org/4de0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4de0 RCSB], [https://www.ebi.ac.uk/pdbsum/4de0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4de0 ProSAT]</span></td></tr> | ||
< | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</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 == | ||
| Line 22: | Line 21: | ||
==See Also== | ==See Also== | ||
*[[Beta-lactamase|Beta-lactamase]] | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Escherichia coli]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Chen | [[Category: Chen Y]] | ||
[[Category: Nichols | [[Category: Nichols DN]] | ||
Latest revision as of 13:45, 6 November 2024
CTX-M-9 class A beta-lactamase complexed with compound 16CTX-M-9 class A beta-lactamase complexed with compound 16
Structural highlights
FunctionPublication Abstract from PubMedThe emergence of CTX-M class A extended-spectrum beta-lactamases poses a serious health threat to the public. We have applied structure-based design to improve the potency of a novel noncovalent tetrazole-containing CTX-M inhibitor (K(i) = 21 muM) more than 200-fold via structural modifications targeting two binding hot spots, a hydrophobic shelf formed by Pro167 and a polar site anchored by Asp240. Functional groups contacting each binding hot spot independently in initial designs were later combined to produce analogues with submicromolar potencies, including 6-trifluoromethyl-3H-benzoimidazole-4-carboxylic acid [3-(1H-tetrazol-5-yl)-phenyl]-amide, which had a K(i) value of 89 nM and reduced the MIC of cefotaxime by 64-fold in CTX-M-9 expressing Escherichia coli . The in vitro potency gains were accompanied by improvements in ligand efficiency (from 0.30 to 0.39) and LipE (from 1.37 to 3.86). These new analogues represent the first nM-affinity noncovalent inhibitors of a class A beta-lactamase. Their complex crystal structures provide valuable information about ligand binding for future inhibitor design. Structure-Based Design of Potent and Ligand-Efficient Inhibitors of CTX-M Class A beta-Lactamase.,Nichols DA, Jaishankar P, Larson W, Smith E, Liu G, Beyrouthy R, Bonnet R, Renslo AR, Chen Y J Med Chem. 2012 Mar 8;55(5):2163-72. Epub 2012 Feb 14. PMID:22296601[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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