title: Proton-translocation by membrane-bound NADH:ubiquinone-oxidoreductase (complex I) through redox-gated ligand conduction.
abstract: For the catalytic mechanism of proton-translocating NADH-dehydrogenase (complex I, EC 1.6.99.3) a number of hypothetical models have been proposed over the last three decades. These models are discussed in the light of recent substantial progress on the structure and function of this very complicated multiprotein complex. Only the high-potential iron-sulfur center N-2 and ubiquinone seem to contribute to the proton-translocating machinery of complex I: Based on the pH dependent midpoint potential of iron-sulfur cluster N-2 and the physical properties of ubiquinone intermediates a novel mechanism is proposed. The model builds on a series of defined chemical reactions taking place at three different ubiquinone-binding sites. Therefore, some aspects of this redox-gated ligand conduction mechanism are reminiscent to the proton-motive Q-cycle. However, its central feature is the abstraction of a proton from ubihydroquinone by a redox-Bohr group associated with iron-sulfur cluster N-2. Thus, in the proposed mechanism proton translocation is driven by a direct linkage between redox dependent protonation of iron-sulfur cluster N-2 and the redox chemistry of ubiquinone.
authors.affiliation: Universitätsklinikum Frankfurt, Zentrum der Biologischen Chemie, Germany. brandt@zbc.klinik.uni-frankfurt.de
authors.forename: U
authors.initials: U
authors.lastname: Brandt
mesh_terms: D000818:Animals; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000378:metabolism; D015640:Ion Channel Gating; D017136:Ion Transport; D007506:Iron-Sulfur Proteins / Q000737:chemistry; D008024:Ligands; D008566:Membranes / Q000201:enzymology; D008954:Models, Biological; D015394:Molecular Structure; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D011522:Protons; D014451:Ubiquinone / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D007506:Iron-Sulfur Proteins; D008024:Ligands; D011522:Protons; D014451:Ubiquinone; D016660:NAD(P)H Dehydrogenase (Quinone)