Crystal Structure of Type II NADH:quinone Oxidoreductase From Caldalkalibacillus Thermarum With an Improved Resolution of 2.15 Å

Acta Crystallogr F Struct Biol Commun. 2017 Oct 1;73(Pt 10):541-549. doi: 10.1107/S2053230X17013073. Epub 2017 Sep 23.

Abstract

Type II NADH:quinone oxidoreductase (NDH-2) is a respiratory enzyme found in the electron-transport chain of many species, with the exception of mammals. It is a 40-70 kDa single-subunit monotopic membrane protein that catalyses the oxidation of NADH and the reduction of quinone molecules via the cofactor FAD. NDH-2 is a promising new target for drug development given its essential role in many bacterial species and intracellular parasites. Only two bacterial NDH-2 structures have been reported and these structures are at moderate resolution (2.3-2.5 Å). In this communication, a new crystallization platform is reported that produced high-quality NDH-2 crystals that diffracted to high resolution (2.15 Å). The high-resolution NDH-2 structure was used for in silico quinone substrate-docking studies to investigate the binding poses of menadione and ubiquinone molecules. These studies revealed that a very limited number of molecular interactions occur at the quinone-binding site of NDH-2. Given that the conformation of the active site is well defined, this high-resolution structure is potentially suitable for in silico inhibitor-compound screening and ligand-docking applications.

Keywords: NDH-2; membrane proteins; quinone binding; respiratory enzymes; type II NADH:quinone oxidoreductase.

MeSH terms

  • Bacillus / enzymology*
  • Binding Sites / physiology
  • Crystallization / methods
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Quinone Reductases / chemistry*
  • Quinone Reductases / metabolism*
  • X-Ray Diffraction / methods

Substances

  • NADH dehydrogenase (quinone)
  • Quinone Reductases

Grant support

This work was funded by Maurice Wilkins Centre for Molecular Biodiscovery grant . Health Research Council of New Zealand grant .