Cytochrome (cyt) bc(1) complex, which is an integral part of the respiratory chain and related energy-conserving systems, has two quinone-binding cavities (Q(o)- and Q(i)-sites), where the substrate participates in electron and proton transfer. Due to its complexity, many of the mechanistic details of the cyt bc(1) function have remained unclear especially regarding the substrate binding at the Q(o)-site. In this work we address this issue by performing extensive atomistic molecular dynamics simulations with the cyt bc(1) complex of Rhodobacter capsulatus embedded in a lipid bilayer. Based on the simulations we are able to show the atom-level binding modes of two substrate forms: quinol (QH(2)) and quinone (Q). The QH(2) binding at the Q(o)-site involves a coordinated water arrangement that produces an exceptionally close and stable interaction between the cyt b and iron sulfur protein subunits. In this arrangement water molecules are positioned suitably in relation to the hydroxyls of the QH(2) ring to act as the primary acceptors of protons detaching from the oxidized substrate. In contrast, water does not have a similar role in the Q binding at the Q(o)-site. Moreover, the coordinated water molecule is also a prime candidate to act as a structural element, gating for short-circuit suppression at the Q(o)-site. (c) 2013 Elsevier B.V. All rights reserved.
B B a - Bioenergetics, 2013, Vol 1827, Issue 6, p. 761-768
Cytochrome bc(1) Molecular dynamics simulation Quinol/quinone Electron transfer Proton transfer Short-circuit suppression ELECTRON-TRANSFER CHAINS IRON-SULFUR PROTEIN Q(O) SITE Q-CYCLE SACCHAROMYCES-CEREVISIAE UBIQUINOL OXIDATION RESPIRATORY-CHAIN QUINOL OXIDATION LIGAND-BINDING BOVINE HEART