View source for 5wag


==ADC-7 in complex with boronic acid transition state inhibitor S06017==
<StructureSection load='5wag' size='340' side='right'caption='[[5wag]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5wag]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Acinetobacter_baumannii Acinetobacter baumannii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WAG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WAG 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]] 1.931&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A0V:1-[[oxidanyl(phosphonooxy)boranyl]methyl]-1,2,3-triazole-4-carboxylic+acid'>A0V</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</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=5wag FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wag OCA], [https://pdbe.org/5wag PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wag RCSB], [https://www.ebi.ac.uk/pdbsum/5wag PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wag ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q6DRA1_ACIBA Q6DRA1_ACIBA] 
<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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5wag" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Acinetobacter baumannii]]
[[Category: Large Structures]]
[[Category: Powers RA]]
[[Category: Wallar BJ]]