COPPER-A OF CYTOCHROME-C-OXIDASE, A NOVEL, LONG-EMBATTLED, BIOLOGICALELECTRON-TRANSFER SITE

This review traces the history of understanding of the Cu-A site in cy tochrome c oxidase (COX) from the beginnings, when few believed that t here 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 Cu1.5+...Cu1.5+ structure through spectr oscopy, recombinant DNA techniques, and crystallography. The critical steps forward in understanding the nature of the Cu-A site are recount ed and the present state (as of the end of 1996) of our knowledge of t he molecular and electronic structure is discussed in some detail. The contributions made through the years by the development of methodolog y and concepts for solving the enigma of Cu-A are emphasized and imped iments, often rooted in contemporary preconceptions and attitudes rath er 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.