Bovine-heart NADH:ubiquinone oxidoreductase is a monomer with 8 Fe-S clusters and 2 FMN groups.
The availability of the amino-acid sequences of a number of mitochondrial and bacterial NADH:ubiquinone oxidoreductases (Complex I), the sequence similarities of five of the essential subunits of Complex I with subunits of [NiFe]hydrogenases and [Fe]hydrogenases, as well as some long-standing controversies about the precise EPR properties and stoichiometries of the iron-sulfur clusters in Complex I have led us to propose a new structural and functional model for this complicated enzyme. The functional unit is a monomer comprising 8 different Fe-S clusters and 2 FMN molecules as prosthetic groups. The electron-input pathway, as well as part of the electron-transfer components, seem largely inherited from bacterial NAD(+)-reducing hydrogenases. The essential electron-transfer components of the electron-output pathway are located in the TYKY subunit. This subunit is proposed to hold both iron-sulfur clusters 2 and to render the enzyme the ability to perform coupled electron transfer. Based on earlier observed similarities (Albracht. S.P.J. (1993) Biochim. Biophys. Acta 1144, 221-224) of the 49 kDa subunit and the PSST subunit with, respectively, the large and small subunits of [NiFe]hydrogenases, it is proposed that the 49 kDa/PSST subunit couple provides Complex I with an ancient proton-transfer pathway.
Albracht
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SP
E.C. Slater Institute, University of Amsterdam, The Netherlands. a31lsiem@chem.uva.nl
Mariette
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de Jong
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D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D019281:Dimerization; D004578:Electron Spin Resonance Spectroscopy; D005486:Flavin Mononucleotide / Q000737:chemistry; D007506:Iron-Sulfur Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D015394:Molecular Structure; D008970:Molecular Weight; D009206:Myocardium / Q000201:enzymology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry*; D011487:Protein Conformation; D011522:Protons; D017386:Sequence Homology, Amino Acid
D007506:Iron-Sulfur Proteins; D011522:Protons; D005486:Flavin Mononucleotide; D016660:NAD(P)H Dehydrogenase (Quinone)