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| | ==ADC-7 in complex with boronic acid transition state inhibitor CR192== | | ==ADC-7 in complex with boronic acid transition state inhibitor CR192== |
| - | <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 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> | + | <table><tr><td colspan='2'>[[5waf]] 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=5WAF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.03Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='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=5waf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5waf OCA], [http://pdbe.org/5waf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5waf RCSB], [http://www.ebi.ac.uk/pdbsum/5waf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5waf ProSAT]</span></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=5waf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5waf OCA], [https://pdbe.org/5waf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5waf RCSB], [https://www.ebi.ac.uk/pdbsum/5waf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5waf ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q6DRA1_ACIBA Q6DRA1_ACIBA] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5waf" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5waf" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Aciba]] | + | [[Category: Acinetobacter baumannii]] |
| - | [[Category: Beta-lactamase]] | + | [[Category: Large Structures]] |
| - | [[Category: Powers, R A]] | + | [[Category: Powers RA]] |
| - | [[Category: Wallar, B J]] | + | [[Category: Wallar BJ]] |
| - | [[Category: Adc-7]]
| + | |
| - | [[Category: Antimicrobial protein]]
| + | |
| - | [[Category: Batsi]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| Structural highlights
Function
Q6DRA1_ACIBA
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bouza AA, Swanson HC, Smolen KA, VanDine AL, Taracila MA, Romagnoli C, Caselli E, Prati F, Bonomo RA, Powers RA, Wallar BJ. Structure-based analysis of boronic acids as inhibitors of Acinetobacter-derived cephalosporinase-7 (ADC-7), a unique class C beta-lactamase. ACS Infect Dis. 2017 Nov 16. doi: 10.1021/acsinfecdis.7b00152. PMID:29144724 doi:http://dx.doi.org/10.1021/acsinfecdis.7b00152
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