Paper Citing NAMD - Abstract
Woelke, Anna Lena; Galstyan, Gegham; Knapp, Ernst-Walter
Lysine 362 in cytochrome c oxidase regulates opening of the K-channel via changes in pK(A) and conformation
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 1837:1998-2003, DEC 2014
The metabolism of aerobic life uses the conversion of molecular oxygen to water as an energy source. This reaction is catalyzed by cytochrome c oxidase (CcO) consuming four electrons and four protons, which move along specific routes. While all four electrons are transferred via the same cofactors to the binuclear reaction center (BNC), the protons take two different routes in the A-type CcO, i.e., two of the four chemical protons consumed in the reaction arrive via the D-channel in the oxidative first half starting after oxygen binding. The other two chemical protons enter via the D-channel in the reductive second half of the reaction cycle. To date, the mechanism behind these separate proton transport pathways has not been understood. In this study, we propose a model that can explain the reaction-step specific opening and closing of the K-channel by conformational and PKA changes of its central lysine 362. Molecular dynamics simulations reveal an upward movement of Lys362 towards the BNC, which had already been supposed by several experimental studies. Redox state-dependent pK(A) calculations provide evidence that Lys362 may protonate transiently, thereby opening the K-channel only in the reductive second half of the reaction cycle. From our results, we develop a model that assigns a key role to Lys362 in the proton gating between the two proton input channels of the A-type CcO. (C) 2014 Published by Elsevier B.V.
