M
Michael N. Gwynn
Researcher at GlaxoSmithKline
Publications - 31
Citations - 4447
Michael N. Gwynn is an academic researcher from GlaxoSmithKline. The author has contributed to research in topics: Topoisomerase & DNA gyrase. The author has an hindex of 19, co-authored 31 publications receiving 3990 citations.
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Journal ArticleDOI
Drugs for bad bugs: confronting the challenges of antibacterial discovery
TL;DR: The experience of evaluating more than 300 genes and 70 high-throughput screening campaigns over a period of 7 years is shared, and what is learned is looked at and how that has influenced GlaxoSmithKline's antibacterials strategy going forward.
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Type IIA topoisomerase inhibition by a new class of antibacterial agents.
Benjamin D. Bax,Pan F. Chan,Drake S. Eggleston,Drake S. Eggleston,Andrew P. Fosberry,Daniel R. Gentry,Fabrice Gorrec,Fabrice Gorrec,Ilaria Giordano,Michael M. Hann,Alan Joseph Hennessy,Martin Hibbs,Jianzhong Huang,Emma J. Jones,Jo J. Jones,Kristin K. Brown,Ceri J. Lewis,Earl May,Earl May,Martin R. Saunders,Onkar M. P. Singh,Claus Spitzfaden,Carol Shen,Anthony Shillings,Andrew J. Theobald,Alexandre Wohlkonig,Alexandre Wohlkonig,Neil D. Pearson,Michael N. Gwynn +28 more
TL;DR: This work provides new insights into the mechanism of topoisomerase action and a platform for structure-based drug design of a new class of antibacterial agents against a clinically proven, but conformationally flexible, enzyme class.
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Identification, Evolution, and Essentiality of the Mevalonate Pathway for Isopentenyl Diphosphate Biosynthesis in Gram-Positive Cocci
E. Imogen Wilding,James R. Brown,Alexander P. Bryant,Alison F. Chalker,David J. Holmes,Karen A. Ingraham,Serban Iordanescu,Chi Y. So,Martin Rosenberg,Michael N. Gwynn +9 more
TL;DR: Phylogenetic and comparative genome analyses suggest that the genes for mevalonate biosynthesis in gram-positive cocci, which are highly divergent from those of mammals, were horizontally transferred from a primitive eukaryotic cell.
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Structural basis of quinolone inhibition of type IIA topoisomerases and target-mediated resistance
Alexandre Wohlkonig,Pan F. Chan,Andrew P. Fosberry,Paul Homes,Jianzhong Huang,Michael Kranz,Vaughan R. Leydon,Timothy J. Miles,Neil D. Pearson,Rajika L. Perera,Anthony Shillings,Michael N. Gwynn,Benjamin D. Bax +12 more
TL;DR: 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 theDNA cleavage domain through chelation of a noncatalytic magnesium ion.
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Challenges of antibacterial discovery revisited
TL;DR: Implementing multiple screening and target identification strategies is recommended for improving the likelihood of discovering new antibacterial compounds that address unmet needs, particularly by the identification of new antibiotic classes with improved tractability and by expanding the predictability of in vitro safety assays.