5waf: Difference between revisions
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<StructureSection load='5waf' size='340' side='right' caption='[[5waf]], [[Resolution|resolution]] 2.03Å' scene=''> | <StructureSection load='5waf' size='340' side='right' caption='[[5waf]], [[Resolution|resolution]] 2.03Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5waf]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WAF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WAF FirstGlance]. <br> | <table><tr><td colspan='2'>[[5waf]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Aciba Aciba]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WAF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WAF FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A0Y:phosphonooxy-[[[4-(1~{H}-1,2,3,4-tetrazol-5-yl)-2-(trifluoromethyl)phenyl]sulfonylamino]methyl]borinic+acid'>A0Y</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=A0Y:phosphonooxy-[[[4-(1~{H}-1,2,3,4-tetrazol-5-yl)-2-(trifluoromethyl)phenyl]sulfonylamino]methyl]borinic+acid'>A0Y</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='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> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Aciba]] | |||
[[Category: Beta-lactamase]] | [[Category: Beta-lactamase]] | ||
[[Category: Powers, R A]] | [[Category: Powers, R A]] | ||
Revision as of 09:43, 20 December 2017
ADC-7 in complex with boronic acid transition state inhibitor CR192ADC-7 in complex with boronic acid transition state inhibitor CR192
Structural highlights
Publication Abstract from PubMedAcinetobacter 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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