Heme-protein crosslinking

Wojciechowski G, Huang L, Ortiz de Montellano PR (2005) Autocatalytic modification of the prosthetic heme of horseradish but not lactoperoxidase by thiocyanate oxidation products. A role for heme-protein covalent crosslinking. J Am Chem Soc 127 15871-15879... 

The respiratory cytochrome c found in the mitochondria of all eukaryotes is a protein with one heme c (Fig. 1) and 103-113 amino acids in a single polypeptide chain with no disulfide crosslinks. It is small and easily extracted from ruptured mitochondria, in contrast to the other protein components of the respiratory chain, which are larger and generally membrane-bound. For this reason, cytochrome c was the first cytochrome to be studied extensively, and has received the most attention from biochemists. The story of its discovery by MacMunn in 1884, its violent rejection by chemist and editor Hoppe-Seyler, subsequent neglect until rediscovered by David Keilin in 1925, and extensive characterization by Hugo Theorell and his school, is a familiar story which need not be repeated here. Good accounts of this history are to be found in reviews... 

Finally, some chemicals and also oxidants have been shown to cause the covalent crosslinking of heme to apo-P450 (ref [877]). Correia s group has characterized the products of the destruction of P450 3A4 with cumene hydroperoxide the information is consistent with a dipyrrolic fragment of heme bound to a fragment of the protein . ... 

Formation of c-type cytochromes requires formation of stereospecific thioether cross-links between the heme and protein. The processes and proteins involved in this post-translational cyt c maturation are being elucidated.The proteins encoded by the cyt c maturation operons have been identified. They are involved in heme transport, chaperoning, and attachment to apocyt c. Although the mechanistic details of cyt c maturation are unknown, the steps will undoubtedly involve a series of axial-ligand exchange reactions as the heme is chaperoned and crosslinked to apocyt c. 

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