4len: Difference between revisions
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==CTX-M-9 in complex with the broad spectrum inhibitor 3-(2- carboxyvinyl)benzo(b)thiophene-2-boronic acid== | |||
<StructureSection load='4len' size='340' side='right'caption='[[4len]], [[Resolution|resolution]] 1.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4len]] 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=4LEN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LEN 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]] 1.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2GK:(2E)-3-[2-(DIHYDROXYBORANYL)-1-BENZOTHIOPHEN-3-YL]PROP-2-ENOIC+ACID'>2GK</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=4len FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4len OCA], [https://pdbe.org/4len PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4len RCSB], [https://www.ebi.ac.uk/pdbsum/4len PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4len ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q9L5C8_ECOLX Q9L5C8_ECOLX] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Production of beta-lactamases (BLs) is the most widespread resistance mechanism adopted by bacteria to fight beta-lactam antibiotics. The substrate spectrum of BLs has become increasingly broad, posing a serious health problem. Thus, there is an urgent need for novel BL inhibitors. Boronic acid transition-state analogues are able to reverse the resistance conferred by class A and C BLs. We describe a boronic acid analogue possessing interesting and potent broad-spectrum activity vs class A and C serine-based BLs. Starting from benzo(b)thiophene-2-boronic acid (BZBTH2B), a nanomolar non-beta-lactam inhibitor of AmpC that can potentiate the activity of a third-generation cephalosporin against AmpC-producing resistant bacteria, we designed a novel broad-spectrum nanomolar inhibitor of class A and C BLs. Structure-based drug design (SBDD), synthesis, enzymology data, and X-ray crystallography results are discussed. We clarified the inhibitor binding geometry responsible for broad-spectrum activity vs serine-active BLs using double mutant thermodynamic cycle studies. | |||
Targeting Class A and C Serine beta-Lactamases with a Broad-Spectrum Boronic Acid Derivative.,Tondi D, Venturelli A, Bonnet R, Pozzi C, Shoichet BK, Costi MP J Med Chem. 2014 Jun 16. PMID:24882105<ref>PMID:24882105</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4len" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli]] | |||
[[Category: Large Structures]] | |||
[[Category: Tondi D]] | |||
Latest revision as of 16:18, 20 September 2023
CTX-M-9 in complex with the broad spectrum inhibitor 3-(2- carboxyvinyl)benzo(b)thiophene-2-boronic acid
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