title: The origin of cluster N2 of the energy-transducing NADH-quinone oxidoreductase: comparisons of phylogenetically related enzymes.
abstract: NADH-quinone (Q) oxidoreductase is a large and complex redox proton pump, which utilizes the free energy derived from oxidation of NADH with lipophilic electron/proton carrier Q to translocate protons across the membrane to generate an electrochemical proton gradient. Although its molecular mechanism is largely unknown, recent biochemical, biophysical, and molecular biological studies have revealed that particular subunits and cofactors play an essential role in the energy-coupling reaction. Based on these latest experimental data, we exhaustively analyzed the sequence information available from evolutionarily related enzymes such as [NiFe] hydrogenases. We found significant and conserved sequence differences in the PSST/Nqo6/NuoB, 49kDa/Nqo4/NuoD, and ND1/Nqo8/NuoH subunit homologs between complex I/NDH-1 and [NiFe] hydrogenases. The alterations, especially in the postulated ligand motif for cluster N2 in the PSST/Nqo6/NuoB subunits, appear to be evolutionarily important in determining the physiological function of complex I/NDH-1. These observations led us to propose a hypothetical evolutionary scheme: during the course of evolution, drastic changes have occurred in the putative cluster N2 binding site in the PSST/Nqo6/NuoB subunit and the progenitors of complex I/NDH-1 have concurrently become to utilize a lipophilic electron/proton carrier such as Q as its physiological substrate. This scheme provides new insights into the structure and function relationship of complex I/NDH-1 and may help us understand its energy-coupling mechanism.
authors.affiliation: Department of Biochemistry and Biophysics, University of Pennsylvania, School of Medicine, Philadelphia 19104-6059, USA. yano@mail.med.upenn.edu
authors.forename: T
authors.initials: T
authors.lastname: Yano
authors.forename: T
authors.initials: T
authors.lastname: Ohnishi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000201:enzymology; D003067:Coenzymes; D004579:Electron Transport; D042967:Electron Transport Complex I; D019143:Evolution, Molecular; D008928:Mitochondria / Q000201:enzymology; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D010084:Oxidation-Reduction; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D003067:Coenzymes; D014451:Ubiquinone; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I; C024989:coenzyme Q10