5o7n

Beta-lactamase VIM-2 in complex with (2R)-1-(2-Benzyl-3-mercaptopropanoyl)piperidine-2-carboxylic acid

spinqualitylabelsall models 5o7n, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5o7n is a 2 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 1.5Å Ligands: 9NK, EDO, FMT, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A173FE28_KLEPN Publication Abstract from PubMed Pathogens, expressing metallo-beta-lactamases (MBLs), become resistant against most beta-lactam antibiotics. Besides the dragging search for new antibiotics, development of MBL inhibitors would be an alternative weapon against resistant bacterial pathogens. Inhibition of resistance enzymes could restore the antibacterial activity of beta-lactams. Various approaches to MBL inhibitors are described; among others, the promising motif of a zinc coordinating thiol moiety is very popular. Nevertheless, since the first report of a thiol-based MBL inhibitor (thiomandelic acid) in 2001, no steps in development of thiol based MBL inhibitors were reported that go beyond clinical isolate testing. In this study, we report on the synthesis and biochemical characterization of thiol-based MBL inhibitors and highlight the challenges behind the development of thiol-based compounds, which exhibit good in vitro activity toward a broad spectrum of MBLs, selectivity against human off-targets, and reasonable activity against clinical isolates. Challenges in the Development of a Thiol-Based Broad-Spectrum Inhibitor for Metallo-beta-Lactamases.,Buttner D, Kramer JS, Klingler FM, Wittmann SK, Hartmann MR, Kurz CG, Kohnhauser D, Weizel L, Bruggerhoff A, Frank D, Steinhilber D, Wichelhaus TA, Pogoryelov D, Proschak E ACS Infect Dis. 2018 Mar 9;4(3):360-372. doi: 10.1021/acsinfecdis.7b00129. Epub, 2017 Dec 12. PMID:29172434 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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