Quinol Oxidation by c-Type Cytochromes: Structural Characterization of the Menaquinol Binding Site of NrfHA

Maria Luisa Rodrigues, Kathryn A. Scott, Mark S.P. Sansom, Inês A.C. Pereira, Margarida Archer

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Membrane-bound cytochrome c quinol dehydrogenases play a crucial role in bacterial respiration by oxidizing menaquinol and transferring electrons to various periplasmic oxidoreductases. In this work, the menaquinol oxidation site of NrfH was characterized by the determination of the X-ray structure of Desulfovibrio vulgaris NrfHA nitrite reductase complex bound to 2-heptyl-4-hydroxyquinoline-N-oxide, which is shown to act as a competitive inhibitor of NrfH quinol oxidation activity. The structure, at 2.8-Å resolution, reveals that the inhibitor binds close to NrfH heme 1, where it establishes polar contacts with two essential residues: Asp89, the residue occupying the heme distal ligand position, and Lys82, a strictly conserved residue. The menaquinol binding cavity is largely polar and has a wide opening to the protein surface. Coarse-grained molecular dynamics simulations suggest that the quinol binding site of NrfH and several other respiratory enzymes lie in the head group region of the membrane, which probably facilitates proton transfer to the periplasm. Although NrfH is not a multi-span membrane protein, its quinol binding site has several characteristics similar to those of quinone binding sites previously described. The data presented here provide the first characterization of the quinol binding site of the cytochrome c quinol dehydrogenase family.

Original languageEnglish
Pages (from-to)341-350
Number of pages10
JournalJournal of Molecular Biology
Volume381
Issue number2
DOIs
Publication statusPublished - 29 Aug 2008

Keywords

  • cytochrome c nitrite reductase NrfHA
  • membrane protein complex
  • NapC/NirT family
  • quinol dehydrogenase
  • quinol inhibitor

Fingerprint

Dive into the research topics of 'Quinol Oxidation by c-Type Cytochromes: Structural Characterization of the Menaquinol Binding Site of NrfHA'. Together they form a unique fingerprint.

Cite this