7cjl

Metallo-Beta-Lactamase VIM-2 in complex with (S)-N-(3-(2H-tetrazol-5-yl)phenyl)-3-mercapto-2-methylpropanamideMetallo-Beta-Lactamase VIM-2 in complex with (S)-N-(3-(2H-tetrazol-5-yl)phenyl)-3-mercapto-2-methylpropanamide

Structural highlights 7cjl is a 2 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 1.789Å Ligands: , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q9K2N0_PSEAI Publication Abstract from PubMed beta-Lactam antibiotic resistance mediated by metallo-beta-lactamases (MBL) has threatened global public health. There are currently no available inhibitors of MBLs for clinical use. We previously reported the ruthenium-catalyzed meta-selective C-H nitration synthesis method, leading to some meta-mercaptopropanamide substituted aryl tetrazoles as new potent MBL inhibitors. Here, we described the structure-activity relationship of meta- and ortho-mercaptopropanamide substituted aryl tetrazoles with clinically relevant MBLs. The resulting most potent compound 13a showed IC50 values of 0.044 muM, 0.396 muM and 0.71 muM against VIM-2, NDM-1 and IMP-1 MBL, respectively. Crystallographic analysis revealed that 13a chelated to active site zinc ions via the thiol group and interacted with the catalytically important residues Asn233 and Tyr67, providing further structural information for the development of thiol based MBL inhibitors. Discovery of mercaptopropanamide-substituted aryl tetrazoles as new broad-spectrum metallo-beta-lactamase inhibitors.,Yan YH, Chen J, Zhan Z, Yu ZJ, Li G, Guo L, Li GB, Wu Y, Zheng Y RSC Adv. 2020 Aug 25;10(52):31377-31384. doi: 10.1039/d0ra06405j. eCollection, 2020 Aug 21. PMID:35520685 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

spinqualitylabelsall models 7cjl, resolution 1.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image