Fig. P1.

The covalent attachment of heme to apocytochrome c to form holocytochrome c in mitochondria requires HCCS. HCCS catalyzes the formation of thioether linkages between the two vinyl groups of heme and the two cysteines of the CysXxxXxxCysHis motif of apocytochrome c. (Upper) Four fundamental steps in the holocytochrome c synthase reaction: heme binding, apocytochrome c recognition, thioether formation, and holocytochrome c release. (Lower) A model of the HCCS:heme:apocytochrome c ternary complex. In this complex heme is coordinated by His154 of HCCS and His19 of apocytochrome c. Additional designated residues in the N terminus of apocytochrome c are important for various steps in the pathway.