The 49-kDa subunit of NADH-ubiquinone oxidoreductase (Complex I) is involved in the binding of piericidin and rotenone, two quinone-related inhibitors

FEBS Lett. 1998 Jul 10;431(1):34-8. doi: 10.1016/s0014-5793(98)00719-4.


Piericidin is a potent inhibitor of the mitochondrial and bacterial type I NADH-ubiquinone oxidoreductases (Complex I) and is considered to bind at or close to the ubiquinone binding site(s) of the enzyme. Piericidin-resistant mutants of the bacterium Rhodobacter capsulatus have been isolated and the present work demonstrates that a single missense mutation at the level of the gene encoding the peripheral 49-kDa/NUOD subunit of Complex I is definitely associated with this resistance. Based on this original observation, we propose a model locating the binding site for piericidin (and quinone) at the interface between the hydrophilic and hydrophobic domains of Complex I.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Binding Sites
  • Drug Resistance, Microbial
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Molecular Sequence Data
  • Mutation
  • NAD(P)H Dehydrogenase (Quinone) / antagonists & inhibitors*
  • NAD(P)H Dehydrogenase (Quinone) / genetics
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • Pyridines / metabolism
  • Pyridines / pharmacology
  • Quinones / chemistry
  • Rhodobacter capsulatus / drug effects*
  • Rhodobacter capsulatus / enzymology
  • Rhodobacter capsulatus / genetics
  • Rotenone / metabolism
  • Rotenone / pharmacology*


  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Pyridines
  • Quinones
  • Rotenone
  • piericidin A
  • NAD(P)H Dehydrogenase (Quinone)

Associated data

  • GENBANK/AF029365