6td1
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of VNRX-5133 (taniborbactam) bound to KPC-2== | |
| + | <StructureSection load='6td1' size='340' side='right'caption='[[6td1]], [[Resolution|resolution]] 1.20Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6td1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae Klebsiella pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6TD1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6TD1 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]] 1.2Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KJK:(3~{R})-3-[2-[4-(2-azanylethylamino)cyclohexyl]ethanoylamino]-2-oxidanyl-3,4-dihydro-1,2-benzoxaborinine-8-carboxylic+acid'>KJK</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6td1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6td1 OCA], [https://pdbe.org/6td1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6td1 RCSB], [https://www.ebi.ac.uk/pdbsum/6td1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6td1 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/BLKPC_KLEPN BLKPC_KLEPN] Hydrolyzes carbapenems, penicillins, cephalosporins and monobactams with varying efficiency. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Klebsiella pneumoniae carbapenemase-2 (KPC-2) is a serine-beta-lactamase (SBL) capable of hydrolysing almost all beta-lactam antibiotics. We compare KPC-2 inhibition by vaborbactam, a clinically-approved monocyclic boronate, and VNRX-5133 (taniborbactam), a bicyclic boronate in late-stage clinical development. Vaborbactam inhibition is slowly reversible, whereas taniborbactam has an off-rate indicating essentially irreversible complex formation and a 15-fold higher on-rate, although both potentiate beta-lactam activity against KPC-2-expressing K. pneumoniae. High resolution X-ray crystal structures reveal closely related binding modes for both inhibitors to KPC-2, with differences apparent only in positioning of the endocyclic boronate ester oxygen. The results indicate the bicyclic boronate scaffold as both an efficient, long-lasting, KPC-2 inhibitor and capable of supporting further iterations that may improve potency against specific enzyme targets and pre-empt the emergence of inhibitor resistant KPC-2 variants. | ||
| - | + | Cyclic boronates as versatile scaffolds for KPC-2 beta-lactamase inhibition.,Tooke CL, Hinchliffe P, Krajnc A, Mulholland AJ, Brem J, Schofield CJ, Spencer J RSC Med Chem. 2020 Jan 10;11(4):491-496. doi: 10.1039/c9md00557a. eCollection , 2020 Apr 1. PMID:33479650<ref>PMID:33479650</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6td1" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Klebsiella pneumoniae]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Hinchliffe P]] | ||
| + | [[Category: Spencer J]] | ||
| + | [[Category: Tooke CL]] | ||
Current revision
Crystal structure of VNRX-5133 (taniborbactam) bound to KPC-2
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