Exploring the ubiquinone binding cavity of respiratory complex I.

摘要: Proton pumping respiratory complex I is a major player in mitochondrial energy conversion. Yet little known about the molecular mechanism of this large membrane protein complex. Understanding details ubiquinone reduction will be prerequisite for elucidating mechanism. Based on recently published partial structure bacterial enzyme, we scanned proposed binding cavity by site-directed mutagenesis strictly aerobic yeast Yarrowia lipolytica. The observed changes catalytic activity and inhibitor sensitivity followed consistent pattern allowed us to define three functionally important regions near ubiquinone-reducing iron-sulfur cluster N2. We identified likely entry path substrate defined region involved within cavity. Finally, were able highlight critical structural motif active site that consisted Tyr-144 49-kDa subunit, surrounded conserved hydrophobic residues.