6b22: Difference between revisions

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 ==Crystal structure OXA-24 beta-lactamase complexed with WCK 4234 by co-crystallization==
-<StructureSection load='6b22' size='340' side='right' caption='[[6b22]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
+<StructureSection load='6b22' size='340' side='right'caption='[[6b22]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6b22]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B22 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B22 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6b22]] is a 1 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=6B22 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B22 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C8Y:(2S,5R)-1-formyl-5-[(sulfooxy)amino]piperidine-2-carbonitrile'>C8Y</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 1.93&#8491;</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=6b22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b22 OCA], [http://pdbe.org/6b22 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b22 RCSB], [http://www.ebi.ac.uk/pdbsum/6b22 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b22 ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C8Y:(2S,5R)-1-formyl-5-[(sulfooxy)amino]piperidine-2-carbonitrile'>C8Y</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=6b22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b22 OCA], [https://pdbe.org/6b22 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b22 RCSB], [https://www.ebi.ac.uk/pdbsum/6b22 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b22 ProSAT]</span></td></tr>
 </table>
-<div style="background-color:#fffaf0;">
+== Function ==
-== Publication Abstract from PubMed ==
+[https://www.uniprot.org/uniprot/Q8RLA6_ACIBA Q8RLA6_ACIBA]
-Limited treatment options exist to combat infections caused by multidrug-resistant (MDR) Gram-negative bacteria possessing broad-spectrum beta-lactamases. The design of novel beta-lactamase inhibitors is of paramount importance. Here, three novel diazabicyclooctanes (DBOs), WCK 5153, zidebactam (WCK 5107), and WCK 4234 (compounds 1-3, respectively), were synthesized and biochemically characterized against clinically important bacteria. Compound 3 inhibited class A, C, and D beta-lactamases with unprecedented k2/ K values against OXA carbapenemases. Compounds 1 and 2 acylated class A and C beta-lactamses rapidly but not the tested OXAs. Compounds 1-3 formed highly stable acyl-complexes as demonstrated by mass spectrometry. Crystallography revealed that 1-3 complexed with KPC-2 adopted a "chair conformation" with the sulfate occupying the carboxylate binding region. The cefepime-2 and meropenem-3 combinations were effective in murine peritonitis and neutropenic lung infection models caused by MDR Acinetobacter baumannii. Compounds 1-3 are novel beta-lactamase inhibitors that demonstate potent cross-class inhibition, and clinical studies targeting MDR infections are warranted.
-Strategic Approaches to Overcome Resistance against Gram-Negative Pathogens Using beta-Lactamase Inhibitors and beta-Lactam Enhancers: Activity of Three Novel Diazabicyclooctanes WCK 5153, Zidebactam (WCK 5107), and WCK 4234.,Papp-Wallace KM, Nguyen NQ, Jacobs MR, Bethel CR, Barnes MD, Kumar V, Bajaksouzian S, Rudin SD, Rather PN, Bhavsar S, Ravikumar T, Deshpande PK, Patil V, Yeole R, Bhagwat SS, Patel MV, van den Akker F, Bonomo RA J Med Chem. 2018 May 10;61(9):4067-4086. doi: 10.1021/acs.jmedchem.8b00091. Epub , 2018 Apr 20. PMID:29627985<ref>PMID:29627985</ref>
+==See Also==
+*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 6b22" style="background-color:#fffaf0;"></div>
-== References ==
-<references/>
 __TOC__
 </StructureSection>
-[[Category: Akker, F van den]]
+[[Category: Acinetobacter baumannii]]
-[[Category: Nguyen, N Q]]
+[[Category: Large Structures]]
-[[Category: Complex]]
+[[Category: Nguyen NQ]]
-[[Category: Hydrolase]]
+[[Category: Van den Akker F]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: Inhibitor]]