TY  - JOUR
A1  - Tocilescu, Maja Aleksandra
A1  - Fendel, Uta
A1  - Zwicker, Klaus
A1  - Kerscher, Stefan
A1  - Brandt, Ulrich
T1  - Exploring the ubiquinone binding cavity of respiratory complex I
T2  - Journal of biological chemistry
N2  - Proton pumping respiratory complex I is a major player in mitochondrial energy conversion. Yet little is known about the molecular mechanism of this large membrane protein complex. Understanding the details of ubiquinone reduction will be prerequisite for elucidating this mechanism. Based on a recently published partial structure of the bacterial enzyme, we scanned the proposed ubiquinone binding cavity of complex I by site-directed mutagenesis in the strictly aerobic yeast Yarrowia lipolytica. The observed changes in catalytic activity and inhibitor sensitivity followed a consistent pattern and allowed us to define three functionally important regions near the ubiquinone-reducing iron-sulfur cluster N2. We identified a likely entry path for the substrate ubiquinone and defined a region involved in inhibitor binding within the cavity. Finally, we were able to highlight a functionally critical structural motif in the active site that consisted of Tyr-144 in the 49-kDa subunit, surrounded by three conserved hydrophobic residues.
Y1  - 2007
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76283
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-762831
SN  - 0021-9258
VL  - 282
IS  - 40
SP  - 29514
EP  - 29520
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -