6r78 | pdb_00006r78

Structure of IMP-13 metallo-beta-lactamase in apo form (loop closed)

spinqualitylabelsall models 6r78, resolution 2.21Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6r78 is a 2 chain structure with sequence from "bacillus_pneumoniae"_(schroeter_1886)_flugge_1886 "bacillus pneumoniae" (schroeter 1886) flugge 1886. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BME, EDO, GOL, NA, PEG, ZN Related: 6r73 Gene: IMP-13 ("Bacillus pneumoniae" (Schroeter 1886) Flugge 1886) Activity: Beta-lactamase, with EC number 3.5.2.6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Multi-drug resistance among Gram-negative bacteria is a major global public health threat. Metallo-beta-lactamases (MBLs) target the most widely-used antibiotic class, the beta-lactams, including the most recent-generation carbapenems. Interspecies spread renders these enzymes a serious clinical threat and there are no clinically-available inhibitors. We present crystal structures of IMP-13, a structurally-uncharacterized MBL from Gram-negative Pseudomonas aerugionasa found in clinical outbreaks globally, and characterize the binding using solution NMR-spectroscopy and molecular-dynamics simulations. Crystal structures of apo IMP-13 and bound to four clinically-relevant carbapenem antibiotics (doripenem, ertapenem, imipenem and meropenem) are presented. Active site plasticity and the active-site loop, where a tryptophan residue stabilizes the antibiotic core scaffold, are essential to the substrate-binding mechanism. The conserved carbapenem scaffold plays the most significant role in IMP-13 binding, explaining the broad substrate specificity. The observed plasticity and substrate-locking mechanism provide opportunities for rational drug design of novel metallo-beta-lactamase inhibitors, essential in the fight against antibiotic resistance. Structure and molecular recognition mechanism of IMP-13 metallo-beta-lactamase.,Softley CA, Zak KM, Bostock MJ, Fino R, Zhou RX, Kolonko M, Mejdi-Nitiu R, Meyer H, Sattler M, Popowicz GM Antimicrob Agents Chemother. 2020 Mar 23. pii: AAC.00123-20. doi:, 10.1128/AAC.00123-20. PMID:32205343 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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