4len: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
''' | ==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
| ||||||||||||
