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4len
From Proteopedia
(Difference between revisions)
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| - | ''' | + | ==CTM-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. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LEN FirstGlance]. <br> | ||
| + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2GK:(2E)-3-[2-(DIHYDROXYBORANYL)-1-BENZOTHIOPHEN-3-YL]PROP-2-ENOIC+ACID'>2GK</scene><br> | ||
| + | <tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4len FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4len OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4len RCSB], [http://www.ebi.ac.uk/pdbsum/4len PDBsum]</span></td></tr> | ||
| + | <table> | ||
| + | <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> | |
| - | + | == References == | |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Beta-lactamase]] | ||
| + | [[Category: Tondi, D.]] | ||
| + | [[Category: Bacterial resistance]] | ||
| + | [[Category: Beta lactamase]] | ||
| + | [[Category: Binding site]] | ||
| + | [[Category: Boronic acid]] | ||
| + | [[Category: Broad spectrum]] | ||
| + | [[Category: Double perturbation cycle analysis]] | ||
| + | [[Category: Drug discovery]] | ||
| + | [[Category: Enzyme inhibitor]] | ||
| + | [[Category: Hydrolase-hydrolase inhibitor complex]] | ||
| + | [[Category: Molecular]] | ||
| + | [[Category: Structure activity relationship]] | ||
| + | [[Category: Structure base drug design]] | ||
| + | [[Category: Thermodynamic]] | ||
Revision as of 07:41, 18 June 2014
CTM-M-9 in complex with the broad spectrum inhibitor 3-(2- carboxyvinyl)benzo(b)thiophene-2-boronic acid
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Categories: Beta-lactamase | Tondi, D. | Bacterial resistance | Beta lactamase | Binding site | Boronic acid | Broad spectrum | Double perturbation cycle analysis | Drug discovery | Enzyme inhibitor | Hydrolase-hydrolase inhibitor complex | Molecular | Structure activity relationship | Structure base drug design | Thermodynamic
