Exploring the quinone/inhibitor-binding pocket in mitochondrial respiratory complex I by chemical biology approaches.

ABSTRACT: NADH-quinone oxidoreductase (respiratory complex I) couples NADH-to-quinone electron transfer to the translocation of protons across the membrane. Even though the architecture of the quinone-access channel in the enzyme has been modeled by X-ray crystallography and cryo-EM, conflicting findings raise the question whether the models fully reflect physiologically relevant states present throughout the catalytic cycle. To gain further insights into the structural features of the binding pocket for quinone/inhibitor, we performed chemical biology experiments using bovine heart sub-mitochondrial particles. We synthesized ubiquinones that are oversized (SF-UQs) or lipid-like (PC-UQs) and are highly unlikely to enter and transit the predicted narrow channel. We found that SF-UQs and PC-UQs can be

SUBMITTER: Uno S 

PROVIDER: S-EPMC6333890 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature