7ayj | pdb_00007ayj

Metallo beta-lactamse Vim-1 with a sulfamoyl inhibitor.

spinqualitylabelsall models 7ayj, resolution 1.21Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7ayj is a 1 chain structure with sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.21Å Ligands: CSD, S9N, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9XAY4_PSEAI Publication Abstract from PubMed Metallo-beta-lactamases (MBLs) can efficiently catalyze the hydrolysis of all classes of beta-lactam antibiotics except monobactams. While serine-beta-lactamase (SBL) inhibitors (e.g., clavulanic acid, avibactam) are established for clinical use, no such MBL inhibitors are available. We report on the synthesis and mechanism of inhibition of N-sulfamoylpyrrole-2-carboxylates (NSPCs) which are potent inhibitors of clinically relevant B1 subclass MBLs, including NDM-1. Crystallography reveals that the N-sulfamoyl NH2 group displaces the dizinc bridging hydroxide/water of the B1 MBLs. Comparison of crystal structures of an NSPC and taniborbactam (VRNX-5133), presently in Phase III clinical trials, shows similar binding modes for the NSPC and the cyclic boronate ring systems. The presence of an NSPC restores meropenem efficacy in clinically derived E. coli and K. pneumoniae blaNDM-1. The results support the potential of NSPCs and related compounds as efficient MBL inhibitors, though further optimization is required for their clinical development. Structural Basis of Metallo-beta-lactamase Inhibition by N-Sulfamoylpyrrole-2-carboxylates.,Farley AJM, Ermolovich Y, Calvopina K, Rabe P, Panduwawala T, Brem J, Bjorkling F, Schofield CJ ACS Infect Dis. 2021 May 18. doi: 10.1021/acsinfecdis.1c00104. PMID:34003651 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

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