4bul

Novel hydroxyl tricyclics (e.g. GSK966587) as potent inhibitors of bacterial type IIA topoisomerases

spinqualitylabelsall models 4bul, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4bul is a 6 chain structure with sequence from Staan. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: AE8, MN Resources: FirstGlance, OCA, RCSB, PDBsum Function [GYRB_STAAN] DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings (By similarity). Publication Abstract from PubMed During the course of our research to find novel mode of action antibacterials, we discovered a series of hydroxyl tricyclic compounds that showed good potency against Gram-positive and Gram-negative pathogens. These compounds inhibit bacterial type IIA topoisomerases. Herein we will discuss structure-activity relationships in this series and report advanced studies on compound 1 (GSK966587) which demonstrates good PK and in vivo efficacy properties. X-ray crystallographic studies were used to provide insight into the structural basis for the difference in antibacterial potency between enantiomers. Novel hydroxyl tricyclics (e.g., GSK966587) as potent inhibitors of bacterial type IIA topoisomerases.,Miles TJ, Hennessy AJ, Bax B, Brooks G, Brown BS, Brown P, Cailleau N, Chen D, Dabbs S, Davies DT, Esken JM, Giordano I, Hoover JL, Huang J, Jones GE, Kusalakumari Sukmar SK, Spitzfaden C, Markwell RE, Minthorn EA, Rittenhouse S, Gwynn MN, Pearson ND Bioorg Med Chem Lett. 2013 Jul 17. pii: S0960-894X(13)00847-0. doi:, 10.1016/j.bmcl.2013.07.013. PMID:23968823 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Gyrase

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