title: Glu-286 rotation and water wire reorientation are unlikely the gating elements for proton pumping in cytochrome C oxidase.
abstract: One of the key unresolved issues regarding proton pumping in cytochrome c oxidase (CcO) is the identity of the gating element that prevents the backflow of protons. In this study, we analyze two popular proposals for this element: isomerization of the key branching residue (Glu-286) and (re)orientation of water molecules in the hydrophobic cavity. Using a multifaceted set of computational analyses that involve CcO embedded in either an implicit or explicit treatment of lipid membrane, we show that neither Glu-286 nor active-site water likely constitutes the gating element. Detailed energetic and structural analyses of the simulation results indicate that the gating-relevant properties of these structural motifs observed in previous work are likely a result of the simplified computational models employed in those studies.
authors: BACTER Graduate Program, University of Wisconsin, Madison, Wisconsin, USA.
authors: Shuo
authors: S
authors: Yang
authors: Qiang
authors: Q
authors: Cui
mesh_terms: D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D003576:Electron Transport Complex IV / Q000737:chemistry*; D018698:Glutamic Acid / Q000737:chemistry*; D015640:Ion Channel Gating / Q000502:physiology*; D011487:Protein Conformation; D017494:Proton Pumps / Q000737:chemistry*; D012242:Rhodobacter sphaeroides / Q000201:enzymology*; D012399:Rotation; D055672:Static Electricity; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry*
chemical_list: D017494:Proton Pumps; D014867:Water; D018698:Glutamic Acid; D003576:Electron Transport Complex IV