8bn6

Pseudomonas aeruginosa DNA gyrase B 24kDa ATPase subdomain complexed with EBL3021Pseudomonas aeruginosa DNA gyrase B 24kDa ATPase subdomain complexed with EBL3021

Structural highlights 8bn6 is a 1 chain structure with sequence from Pseudomonas aeruginosa PAO1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed A new series of dual low nanomolar benzothiazole inhibitors of bacterial DNA gyrase and topoisomerase IV were developed. The resulting compounds show excellent broad-spectrum antibacterial activities against Gram-positive Enterococcus faecalis, Enterococcus faecium and multidrug resistant (MDR) Staphylococcus aureus strains [best compound minimal inhibitory concentrations (MICs): range, <0.03125-0.25 mug/mL] and against the Gram-negatives Acinetobacter baumannii and Klebsiella pneumoniae (best compound MICs: range, 1-4 mug/mL). Lead compound 7a was identified with favorable solubility and plasma protein binding, good metabolic stability, selectivity for bacterial topoisomerases, and no toxicity issues. The crystal structure of 7a in complex with Pseudomonas aeruginosa GyrB24 revealed its binding mode at the ATP-binding site. Expanded profiling of 7a and 7h showed potent antibacterial activity against over 100 MDR and non-MDR strains of A. baumannii and several other Gram-positive and Gram-negative strains. Ultimately, in vivo efficacy of 7a in a mouse model of vancomycin-intermediate S. aureus thigh infection was also demonstrated. New Dual Inhibitors of Bacterial Topoisomerases with Broad-Spectrum Antibacterial Activity and In Vivo Efficacy against Vancomycin-Intermediate Staphylococcus aureus.,Durcik M, Cotman AE, Toplak Z, Mozina S, Skok Z, Szili PE, Czikkely M, Maharramov E, Vu TH, Piras MV, Zidar N, Ilas J, Zega A, Trontelj J, Pardo LA, Hughes D, Huseby D, Berruga-Fernandez T, Cao S, Simoff I, Svensson R, Korol SV, Jin Z, Vicente F, Ramos MC, Mundy JEA, Maxwell A, Stevenson CEM, Lawson DM, Glinghammar B, Sjostrom E, Bohlin M, Oreskar J, Alver S, Janssen GV, Sterk GJ, Kikelj D, Pal C, Tomasic T, Peterlin Masic L J Med Chem. 2023 Mar 23;66(6):3968-3994. doi: 10.1021/acs.jmedchem.2c01905. Epub , 2023 Mar 6. PMID:36877255 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Gyrase 3D Structures

spinqualitylabelsall models 8bn6, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image