Simon Brown
Massey University, Palmerston North, New Zealand
Cytochrome c oxidase is a member of a large superfamily of protonmotive terminal oxidases and is found in eukaryotes and some prokaryotes. The eukaryotic enzyme is located in the inner mitochondrial membrane, oxidises ferrocytochrome c and generally has 12-15 subunits, of which three (subunits I, II and III) are mitochondrially encoded, and 4 redox centres. Many prokaryotes have quinol oxidases, which oxidise quinol and generally have 3-4 subunits and 3 redox centres. In spite of these differences, they have similar catalytic and ligand-binding (CN, CO) properties, which, together with the sequence homology, has led to the assumption that the structure of subunit I is largely conserved amongst the members of the superfamily. The three redox centres common to all these enzymes are ligated by residues in subunit I and the ligands for each of these have been identified using site-directed mutants of the quinol oxidase from Escherichia coli, cytochrome bo (Lemieux et al., 1992, Brown et al., 1994).
However, the protein sequence of subunit I of terminal protonmotive oxidases is more conserved on the positive side of the membrane than the negative side of the membrane (Brown et al., 1993). I have argued that this is because the large bulk of these proteins protruding into the positive phase constrains the acceptable range of conformations of these regions of the polypeptide. Comparison of those enzymes which oxidise ferrocytochrome c with those enzymes which oxidise quinol confirms that there are several features in the subunit I sequences consistent with the differences in their structure and function.
References
Brown, S., Moody, A.J., Mitchell, R. & Rich, P.R. (1993) FEBS Lett. 316, 216-223
Brown, S., Rumbley, J.N., Moody, A.J., Thomas, J.W., Gennis, R.B. & Rich, P.R. (1994) Biochim. Biophys. Acta 1183, 521-532
Lemieux, L.J., Calhoun, M.W., Thomas, J.W., Ingledew, W.J. and Gennis, R.B. (1992) J. Biol. Chem. 267, 2105-2113
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