Structural insight into the quinolone-DNA cleavage complex of type IIA topoisomerases

被引：234

作者：

Laponogov, Ivan ^{[1
,2
]}

Sohi, Maninder K. ^{[2
]}

Veselkov, Dennis A. ^{[2
]}

Pan, Xiao-Su ^{[1
]}

Sawhney, Ritica ^{[1
]}

Thompson, Andrew W. ^{[3
]}

McAuley, Katherine E. ^{[4
]}

Fisher, L. Mark ^{[1
]}

Sanderson, Mark R. ^{[2
]}

机构：

[1] Univ London, Mol & Metab Signalling Ctr, Mol Genet Grp, Div Basic Med Sci, London, England

[2] Kings Coll London, Randall Div Cell & Mol Biophys, London WC2R 2LS, England

[3] Synchrotron SOLEIL, Gif Sur Yvette, France

[4] Diamond Light Source, Beamline IO3, Didcot, Oxon, England

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2009年 / 16卷 / 06期

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

STREPTOCOCCUS-PNEUMONIAE; CRYSTAL-STRUCTURE; GYRASE; RESISTANCE; IV; MODEL; MUTATIONS; MECHANISM; BINDING; PROTEIN;

D O I：

10.1038/nsmb.1604

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Type II topoisomerases alter DNA topology by forming a covalent DNA-cleavage complex that allows DNA transport through a double-stranded DNA break. We present the structures of cleavage complexes formed by the Streptococcus pneumoniae ParC breakage-reunion and ParE TOPRIM domains of topoisomerase IV stabilized by moxifloxacin and clinafloxacin, two antipneumococcal fluoroquinolones. These structures reveal two drug molecules intercalated at the highly bent DNA gate and help explain antibacterial quinolone action and resistance.

引用

页码：667 / 669

页数：3

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