Structural basis of quinolone inhibition of type IIA topoisomerases and target-mediated resistance

被引：232

作者：

Wohlkonig, Alexandre ^{[1
]}

Chan, Pan F. ^{[2
]}

Fosberry, Andrew P. ^{[1
]}

Homes, Paul ^{[1
]}

Huang, Jianzhong ^{[2
]}

Kranz, Michael ^{[1
]}

Leydon, Vaughan R. ^{[1
]}

Miles, Timothy J. ^{[3
]}

Pearson, Neil D. ^{[2
]}

Perera, Rajika L. ^{[1
]}

Shillings, Anthony J. ^{[1
]}

Gwynn, Michael N.

Bax, Benjamin D. ^{[1
]}

机构：

[1] GlaxoSmithKline, Med Res Ctr, Platform Technol & Sci, Stevenage, Herts, England

[2] GlaxoSmithKline, Infect Dis Ctr Excellence Drug Discovery, Antibacterial Discovery Performance Unit, Collegeville, PA USA

[3] GlaxoSmithKline, Infect Dis Ctr Excellence Drug Discovery, Antibacterial Discovery Performance Unit, Med Res Ctr, Stevenage, Herts, England

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2010年 / 17卷 / 09期

基金：

英国惠康基金;

关键词：

DNA CLEAVAGE; BAD BUGS; MAGNESIUM; DRUGS;

D O I：

10.1038/nsmb.1892

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Quinolone antibacterials have been used to treat bacterial infections for over 40 years. A crystal structure of moxifloxacin in complex with Acinetobacter baumannii topoisomerase IV now shows the wedge-shaped quinolone stacking between base pairs at the DNA cleavage site and binding conserved residues in the DNA cleavage domain through chelation of a noncatalytic magnesium ion. This provides a molecular basis for the quinolone inhibition mechanism, resistance mutations and invariant quinolone antibacterial structural features.

引用

页码：1152 / 1153

页数：2

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