Isolation of a human cDNA for heme A:farnesyltransferase by functional complementation of a yeast cox10 mutant.

Abstract

We have cloned the human homolog of the Saccharomyces cereviswe COXIO gene by functional complementation of a yeast coxIO null mutant. The 2.8-kb cDNA encoding the human heme A:farnesyltransferase codes for a 443-aa protein with high homology to the yeast and bacterial farnesylases. The human COX10 homolog, however, does not complement the mutation as efficiently as the yeast COX10 protein, likely due to the heterologous environment. PCR amplification and Southern analysis confirm the existence of a large mRNA for the human protein, with an unusually long 3' untranslated region. This done can now be used to screen patients with inherited deficiencies in cytochrome oxidase in which the mutations remain unidentified and are likely to reside in a protein influencing the assembly of the enzyme.

Formation of the Redox Cofactor Centers during Cox1 Maturation in Yeast Cytochrome Oxidase

“…Heme a synthesis is catalyzed by two successive enzymes, Cox10 and Cox15, that reside within the inner membrane (IM) (7,21). Cox10 is a farnesyl transferase that converts protoheme to heme o. Cox15 subsequently catalyzes the oxidation of the C-8 heme methyl group in a reaction that involves matrix Yah1 ferredoxin and Arh1 ferredoxin reductase (8,11).…”

The Mitochondrial Oxidative Phosphorylation Proteome of Chlamydomonas reinhardtii Deduced from the Genome Sequencing Project

“…The COX11, COX17, COX19, COX23, SCO1, and SCO2 proteins play a role in copper delivery to cytochrome c oxidase (Nobrega et al, 2002;Barros et al, 2004;Horng et al, 2004;Leary et al, 2004), whereas COX10 and COX15 are required for heme a biosynthesis (Glerum and Tzagoloff, 1994;Barros and Tzagoloff, 2002). Homologs of all these proteins are present in C. reinhardtii, mammals, and plants (Table I).…”

Cloning and Characterization of PET100, a Gene Required for the Assembly of Yeast Cytochrome c Oxidase

“…COX10p has been proposed to be a farnesyl transferase that participates in the farnesylation of the vinyl group at carbon 2 of protoheme b, which is a direct precursor to heme A (19). Homologues of the COX10 gene have been found in bacteria (56 -59) and in humans (60). COX11p has been proposed to be involved in the paired oxidation/oxygenation step that converts the methyl group at carbon 8 of the heme ring to a formyl group (19).…”