6t3d

Crystal structure of AmpC from E.coliCrystal structure of AmpC from E.coli

Structural highlights 6t3d is a 1 chain structure with sequence from Escherichia coli K-12. 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: , , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AMPC_ECOLI This protein is a serine beta-lactamase with a substrate specificity for cephalosporins. Publication Abstract from PubMed Resistance to beta-lactam antibacterials, importantly via production of beta-lactamases, threatens their widespread use. Bicyclic boronates show promise as clinically useful, dual-action inhibitors of both serine- (SBL) and metallo- (MBL) beta-lactamases. In combination with cefepime, the bicyclic boronate taniborbactam is in phase 3 clinical trials for treatment of complicated urinary tract infections. We report kinetic and crystallographic studies on the inhibition of AmpC, the class C betalactamase from Escherichia coli, by bicyclic boronates, including taniborbactam, with different C-3 side chains. The combined studies reveal that an acylamino side chain is not essential for potent AmpC inhibition by active site binding bicyclic boronates. The tricyclic form of taniborbactam was observed bound to the surface of crystalline AmpC, but not at the active site, where the bicyclic form was observed. Structural comparisons reveal insights into why active site binding of a tricyclic form has been observed with the NDM-1 MBL, but not with other studied beta-lactamases. Together with reported studies on the structural basis of inhibition of class A, B and D betalactamases, our data support the proposal that bicyclic boronates are broad-spectrum betalactamase inhibitors that work by mimicking a high energy 'tetrahedral' intermediate. These results suggest further SAR guided development could improve the breadth of clinically useful beta-lactamase inhibition. Bicyclic Boronates as Potent Inhibitors of AmpC, the Class C beta-Lactamase from Escherichia coli.,Lang PA, Parkova A, Leissing TM, Calvopina K, Cain R, Krajnc A, Panduwawala TD, Philippe J, Fishwick CWG, Trapencieris P, Page MGP, Schofield CJ, Brem J Biomolecules. 2020 Jun 12;10(6). pii: biom10060899. doi: 10.3390/biom10060899. PMID:32545682 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

spinqualitylabelsall models 6t3d, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image