4de0: Difference between revisions

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-[[Image:4de0.jpg|left|200px]]
-<!--
+==CTX-M-9 class A beta-lactamase complexed with compound 16==
-The line below this paragraph, containing "STRUCTURE_4de0", creates the "Structure Box" on the page.
+<StructureSection load='4de0' size='340' side='right'caption='[[4de0]], [[Resolution|resolution]] 1.12&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<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>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.12&#8491;</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>
-{{STRUCTURE_4de0|  PDB=4de0  |  SCENE=  }}
+<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>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q9L5C8_ECOLX Q9L5C8_ECOLX]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The 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.
-===CTX-M-9 class A beta-lactamase complexed with compound 16===
+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<ref>PMID:22296601</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4de0" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_22296601}}, adds the Publication Abstract to the page
+*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 22296601 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_22296601}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[4de0]] is a 2 chain structure with sequence from [http://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].
-==Reference==
-<ref group="xtra">PMID:022296601</ref><references group="xtra"/>
-[[Category: Beta-lactamase]]
 [[Category: Escherichia coli]]
-[[Category: Chen, Y.]]
+[[Category: Large Structures]]
-[[Category: Nichols, D N.]]
+[[Category: Chen Y]]
-[[Category: Ctx-m]]
+[[Category: Nichols DN]]
-[[Category: Fragment]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: Hydrolase/hydrolase inhibitor]]
-[[Category: Molecular docking]]