Copper A of Cytochrome c Oxidase, A Novel, Long‐Embattled, Biological Electron‐Transfer Site

Abstract

This review traces the history of understanding of the CU, site in cytochrome c oxidase (COX) from the beginnings, when few believed that there was any significant Cu in COX, to the verification of three atoms Cu/monomer and to the final identification of the site as a dinuclear, Cys-bridged average valence ... Cu' 5+ structure through spectroscopy, recombinant DNA techniques, and crystallography. The CUM+ critical steps forward in understanding the nature of the Cu, site are recounted and the present state (as of the end of 1996) of our knowledge of the molecular and electronic structure is discussed in some detail. The contributions made through the years by the development of methodology and concepts for solving the enigma of Cu, are emphasized and impediments, often rooted in contemporary preconceptions and attitudes rather than solid data, are mentioned, which discouraged the exploitation of early valuable clues. Finally, analogies in construction principles of polynuclear Cu-S and Fe-S proteins are pointed out.

COX23, a Homologue of COX17, Is Required for Cytochrome Oxidase Assembly

“…The copper in cytochrome oxidase is associated with two separate catalytic sites (1,2). Two of the coppers form the Cu A center in subunit 2 (Cox2p).…”

“…The third copper, referred to as Cu B , is in electronic equilibrium with the heme a of cytochrome a 3 in subunit 1 (Cox1p). The Cu A center is located in a carboxyl-terminal domain of Cox2p that protrudes into the intermembrane space of mitochondria where it acts as the initial acceptor of electrons from cytochrome c (1,2). Acquisition of copper for the Cu A center of Cox2p has been shown to depend on at least two proteins (3)(4)(5).…”

Crystal structure of aqua-N-(2-hydroxyphenylmethenylimino)-1,5-diamine-3-azapentanecopper(II) chloride, [(C11H16N3O)Cu(H2O)]Cl

“…Among them are two classes of copper-containing metalloproteins responsible for rapid intra-and intermolecular electron transfer in biological systems: those containing mononuclear blue copper sites [1][2][3][4][5] and those containing dinuclear CuA centers [6][7][8]. The blue copper (or type I Cu) center, is found in plastocyanin, azurin, stellacyanin, and the multicopper oxidases.…”

Crystal structure of aqua-N-(2-hydroxyphenylmethenylimino)-1,5-diamine-3-azapentanecopper(II) chloride, [(C11H16N3O)Cu(H2O)]Cl

“…Among them are two classes of copper-containing metalloproteins responsible for rapid intra-and intermolecular electron transfer in biological systems: those containing mononuclear blue copper sites [1][2][3][4][5] and those containing dinuclear CuA centers [6][7][8]. The blue copper (or type I Cu) center, is found in plastocyanin, azurin, stellacyanin, and the multicopper oxidases.…”