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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-A 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 publication

DOI

10.1016/j.jmb.2008.05.066

Type

Journal article

Journal

J Mol Biol

Publication Date

29/08/2008

Volume

381

Pages

341 - 350

Keywords

Bacterial Proteins, Binding Sites, Computer Simulation, Crystallography, X-Ray, Cytochromes a1, Cytochromes c1, Desulfovibrio vulgaris, Hydroxyquinolines, Models, Molecular, Molecular Sequence Data, Nitrate Reductases, Oxidation-Reduction, Protein Structure, Secondary, Protein Structure, Tertiary, Thermodynamics