Transition Metals in Biochemistry Molecular architecture of the proton diode of cytochrome c oxidase

Abstract CytcO (cytochrome c oxidase) is a membrane-bound multisubunit protein which catalyses the reduction of O 2 to H 2 O. The reaction is arranged topographically so that the electrons and protons are taken from opposite sides of the membrane and, in addition, it is also linked to proton pumping across the membrane. Thus the CytcO moves an equivalent of two positive charges across the membrane per electron transferred to O 2 . Proton transfer through CytcO must be controlled by the protein to prevent leaks, which would dissipate the proton electrochemical gradient that is maintained across the membrane. The molecular mechanism by which the protein controls the unidirectionality of proton-transfer (cf. proton diode) reactions and energetically links electron transfer to proton translocation is not known. This short review summarizes selected results from studies aimed at understanding this mechanism, and we discuss a possible mechanistic principle utilized by the oxidase to pump protons. Structure and function of CytcO (cytochrome c oxidase) CytcO catalyses the oxidation of four molecules of cytochrome c and the reduction of O 2 to H 2 O (eqn 1a). The electrons are donated from the relatively positive (P-) side of the membrane, while the protons (referred to as substrate protons) are taken up from the relatively negative (N-) side of the membrane The subscripts P and N refer to the positively and negatively charged sides of the membrane respectively, and c is cytochrome c. The most commonly studied CytcOs (e.g. CytcOs from mitochondria, Rhodobacter sphaeroides and Paracoccus denitrificans) carry four redox-active cofactor