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From the same journal

The mechanism of catalysis by type-II NADH: quinone oxidoreductases

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  • James N Blaza
  • Hannah R Bridges
  • David Aragão
  • Elyse A Dunn
  • Adam Heikal
  • Gregory M Cook
  • Yoshio Nakatani
  • Judy Hirst


Publication details

JournalScientific Reports
DateAccepted/In press - 1 Dec 2016
DatePublished (current) - 9 Jan 2017
Original languageEnglish


Type II NADH:quinone oxidoreductase (NDH-2) is central to the respiratory chains of many organisms. It is not present in mammals so may be exploited as an antimicrobial drug target or used as a substitute for dysfunctional respiratory complex I in neuromuscular disorders. NDH-2 is a single-subunit monotopic membrane protein with just a flavin cofactor, yet no consensus exists on its mechanism. Here, we use steady-state and pre-steady-state kinetics combined with mutagenesis and structural studies to determine the mechanism of NDH-2 from Caldalkalibacillus thermarum. We show that the two substrate reactions occur independently, at different sites, and regardless of the occupancy of the partner site. We conclude that the reaction pathway is determined stochastically, by the substrate/product concentrations and dissociation constants, and can follow either a ping-pong or ternary mechanism. This mechanistic versatility provides a unified explanation for all extant data and a new foundation for the development of therapeutic strategies.

Bibliographical note

© The Author(s) 2017

    Research areas

  • Bacillales, Binding Sites, Catalysis, Dinitrocresols/metabolism, Kinetics, Protein Binding, Quinone Reductases/chemistry, Reactive Oxygen Species/metabolism

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