5cdq | pdb_00005cdq

2.95A structure of Moxifloxacin with S.aureus DNA gyrase and DNA

spinqualitylabelsall models 5cdq, resolution 2.95Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5cdq is a 12 chain structure with sequence from Staan. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, MFX, MG NonStd Res: PTR Gene: gyrA, SA0006 (STAAN), gyrB, SA0005 (STAAN) Activity: DNA topoisomerase (ATP-hydrolyzing), with EC number 5.99.1.3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [GYRA_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.[HAMAP-Rule:MF_01897] [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 New antibacterials are needed to tackle antibiotic-resistant bacteria. Type IIA topoisomerases (topo2As), the targets of fluoroquinolones, regulate DNA topology by creating transient double-strand DNA breaks. Here we report the first co-crystal structures of the antibacterial QPT-1 and the anticancer drug etoposide with Staphylococcus aureus DNA gyrase, showing binding at the same sites in the cleaved DNA as the fluoroquinolone moxifloxacin. Unlike moxifloxacin, QPT-1 and etoposide interact with conserved GyrB TOPRIM residues rationalizing why QPT-1 can overcome fluoroquinolone resistance. Our data show etoposide's antibacterial activity is due to DNA gyrase inhibition and suggests other anticancer agents act similarly. Analysis of multiple DNA gyrase co-crystal structures, including asymmetric cleavage complexes, led to a 'pair of swing-doors' hypothesis in which the movement of one DNA segment regulates cleavage and religation of the second DNA duplex. This mechanism can explain QPT-1's bacterial specificity. Structure-based strategies for developing topo2A antibacterials are suggested. Structural basis of DNA gyrase inhibition by antibacterial QPT-1, anticancer drug etoposide and moxifloxacin.,Chan PF, Srikannathasan V, Huang J, Cui H, Fosberry AP, Gu M, Hann MM, Hibbs M, Homes P, Ingraham K, Pizzollo J, Shen C, Shillings AJ, Spitzfaden CE, Tanner R, Theobald AJ, Stavenger RA, Bax BD, Gwynn MN Nat Commun. 2015 Dec 7;6:10048. doi: 10.1038/ncomms10048. PMID:26640131 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Gyrase 3D Structures

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