6td1

Crystal structure of VNRX-5133 (taniborbactam) bound to KPC-2

spinqualitylabelsall models 6td1, resolution 1.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6td1 is a 1 chain structure with sequence from Klebsiella pneumoniae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.2Å Ligands: GOL, KJK, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BLKPC_KLEPN Hydrolyzes carbapenems, penicillins, cephalosporins and monobactams with varying efficiency. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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