Literature DB >> 26457513

Crystallization and initial crystallographic analysis of covalent DNA-cleavage complexes of Staphyloccocus aureus DNA gyrase with QPT-1, moxifloxacin and etoposide.

Velupillai Srikannathasan1, Alexandre Wohlkonig1, Anthony Shillings1, Onkar Singh1, Pan F Chan2, Jianzhong Huang2, Michael N Gwynn2, Andrew P Fosberry1, Paul Homes1, Martin Hibbs1, Andrew J Theobald1, Claus Spitzfaden1, Benjamin D Bax1.   

Abstract

Fluoroquinolone drugs such as moxifloxacin kill bacteria by stabilizing the normally transient double-stranded DNA breaks created by bacterial type IIA topoisomerases. Previous crystal structures of Staphylococcus aureus DNA gyrase with asymmetric DNAs have had static disorder (with the DNA duplex observed in two orientations related by the pseudo-twofold axis of the complex). Here, 20-base-pair DNA homoduplexes were used to obtain crystals of covalent DNA-cleavage complexes of S. aureus DNA gyrase. Crystals with QPT-1, moxifloxacin or etoposide diffracted to between 2.45 and 3.15 Å resolution. A G/T mismatch introduced at the ends of the DNA duplexes facilitated the crystallization of slightly asymmetric complexes of the inherently flexible DNA-cleavage complexes.

Entities:  

Keywords:  DNA complex; DNA gyrase; etoposide; fluoroquinolone; topoisomerase

Mesh：

Substances：

Year:  2015        PMID： 26457513      PMCID： PMC4601586          DOI： 10.1107/S2053230X15015290

Source DB:  PubMed          Journal:  Acta Crystallogr F Struct Biol Commun        ISSN： 2053-230X            Impact factor:   1.056


  20 in total

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2.  Discovery and characterization of QPT-1, the progenitor of a new class of bacterial topoisomerase inhibitors.

Authors:  Alita A Miller; Gordon L Bundy; John E Mott; Jill E Skepner; Timothy P Boyle; Douglas W Harris; Alexander E Hromockyj; Keith R Marotti; Gary E Zurenko; Jennifer B Munzner; Michael T Sweeney; Gary F Bammert; Judith C Hamel; Charles W Ford; Wei-Zhu Zhong; David R Graber; Gary E Martin; Fusen Han; Lester A Dolak; Eric P Seest; J Craig Ruble; Gregg M Kamilar; John R Palmer; Lee S Banitt; Alexander R Hurd; Michael R Barbachyn
Journal:  Antimicrob Agents Chemother       Date:  2008-06-02       Impact factor: 5.191

Review 3.  Moving one DNA double helix through another by a type II DNA topoisomerase: the story of a simple molecular machine.

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  11 in total

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3.  Thiophene antibacterials that allosterically stabilize DNA-cleavage complexes with DNA gyrase.

Authors:  Pan F Chan; Thomas Germe; Benjamin D Bax; Jianzhong Huang; Reema K Thalji; Eric Bacqué; Anna Checchia; Dongzhao Chen; Haifeng Cui; Xiao Ding; Karen Ingraham; Lynn McCloskey; Kaushik Raha; Velupillai Srikannathasan; Anthony Maxwell; Robert A Stavenger
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4.  Structure of a quinolone-stabilized cleavage complex of topoisomerase IV from Klebsiella pneumoniae and comparison with a related Streptococcus pneumoniae complex.

Authors:  Dennis A Veselkov; Ivan Laponogov; Xiao-Su Pan; Jogitha Selvarajah; Galyna B Skamrova; Arthur Branstrom; Jana Narasimhan; Josyula V N Vara Prasad; L Mark Fisher; Mark R Sanderson
Journal:  Acta Crystallogr D Struct Biol       Date:  2016-03-24       Impact factor: 7.652

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Journal:  Molecules       Date:  2019-05-04       Impact factor: 4.411

Review 7.  DNA Topoisomerase Inhibitors: Trapping a DNA-Cleaving Machine in Motion.

Authors:  Benjamin D Bax; Garib Murshudov; Anthony Maxwell; Thomas Germe
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9.  Exploring the active site of the Streptococcus pneumoniae topoisomerase IV-DNA cleavage complex with novel 7,8-bridged fluoroquinolones.

Authors:  Ivan Laponogov; Xiao-Su Pan; Dennis A Veselkov; Ryan T Cirz; Allan Wagman; Heinz E Moser; L Mark Fisher; Mark R Sanderson
Journal:  Open Biol       Date:  2016-09       Impact factor: 6.411

10.  Structural basis of DNA gyrase inhibition by antibacterial QPT-1, anticancer drug etoposide and moxifloxacin.

Authors:  Pan F Chan; Velupillai Srikannathasan; Jianzhong Huang; Haifeng Cui; Andrew P Fosberry; Minghua Gu; Michael M Hann; Martin Hibbs; Paul Homes; Karen Ingraham; Jason Pizzollo; Carol Shen; Anthony J Shillings; Claus E Spitzfaden; Robert Tanner; Andrew J Theobald; Robert A Stavenger; Benjamin D Bax; Michael N Gwynn
Journal:  Nat Commun       Date:  2015-12-07       Impact factor: 14.919
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