5wac: Difference between revisions
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==ADC-7 in complex with boronic acid transition state inhibitor CR157== | |||
<StructureSection load='5wac' size='340' side='right' caption='[[5wac]], [[Resolution|resolution]] 2.06Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5wac]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WAC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WAC FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A1M:phosphonooxy-[[[4-(1~{H}-1,2,3,4-tetrazol-5-yl)phenyl]sulfonylamino]methyl]borinic+acid'>A1M</scene></td></tr> | |||
<tr id='activity'><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 id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5wac FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wac OCA], [http://pdbe.org/5wac PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wac RCSB], [http://www.ebi.ac.uk/pdbsum/5wac PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wac ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Acinetobacter baumannii is a multidrug resistant pathogen that infects more than 12,000 patients each year in the US. Much of the resistance to beta-lactam antibiotics in Acinetobacter spp. is a result of class C beta-lactamases known as Acinetobacter-derived cephalosporinases (ADCs). ADCs are unaffected by clinically used -lactam-based beta-lactamase inhibitors. In this study, five boronic acid transition state analog inhibitors (BATSIs) were evaluated for inhibition of the class C cephalosporinase ADC-7. Our goal was to explore the properties of BATSIs designed to probe the R1 binding site. Ki values ranged from low micromolar to sub-nanomolar, and circular dichroism (CD) demonstrated that each inhibitor stabilizes the beta-lactamase-inhibitor complexes. Additionally, X-ray crystal structures of ADC-7 in complex with five inhibitors were determined (resolutions from 1.80-2.09 A). In the ADC-7/CR192 complex, the BATSI with the lowest Ki (0.45 nM) and greatest DeltaTm (+9 degrees C), a trifluoromethyl substituent interacts with Arg340. Arg340 is unique to ADCs and may play an important role in the inhibition of ADC-7. The ADC-7/BATSI complexes determined in this study shed light into the unique recognition sites in ADC enzymes, and also offer insight into further structure-based optimization of these inhibitors. | |||
Structure-based analysis of boronic acids as inhibitors of Acinetobacter-derived cephalosporinase-7 (ADC-7), a unique class C beta-lactamase.,Bouza AA, Swanson HC, Smolen KA, VanDine AL, Taracila MA, Romagnoli C, Caselli E, Prati F, Bonomo RA, Powers RA, Wallar BJ ACS Infect Dis. 2017 Nov 16. doi: 10.1021/acsinfecdis.7b00152. PMID:29144724<ref>PMID:29144724</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Wallar, B | <div class="pdbe-citations 5wac" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Beta-lactamase]] | |||
[[Category: Powers, R A]] | |||
[[Category: Wallar, B J]] | |||
[[Category: Adc-7]] | |||
[[Category: Antimicrobial protein]] | |||
[[Category: Batsi]] | |||
[[Category: Hydrolase-hydrolase inhibitor complex]] | |||
[[Category: Inhibitor]] | |||
