Computational prediction and in vitro analysis of potential physiological ligands of the bile acid binding site in cytochrome c oxidase.

ABSTRACT: A conserved bile acid site has been crystallographically defined in the membrane domain of mammalian and Rhodobacter sphaeroides cytochrome c oxidase (RsCcO). Diverse amphipathic ligands were shown previously to bind to this site and affect the electron transfer equilibrium between heme a and a3 cofactors by blocking the K proton uptake path. Current studies identify physiologically relevant ligands for the bile acid site using a novel three-pronged computational approach: ROCS comparison of ligand shape and electrostatics, SimSite3D comparison of ligand binding site features, and SLIDE screening of potential ligands by docking. Identified candidate ligands include steroids, nicotinamides, flavins, nucleotides, retinoic acid, and thyroid hormones, which are predicted to make key protein co

SUBMITTER: Buhrow L 

PROVIDER: S-EPMC3859723 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature