Cytochrome heme active site

Loew GH, Harris DL. 2000. Role of the heme active site and protein environment in structure, spectra and function of the cytochrome P450s. Chem Rev 100 407. 

Figure 9.3. The cytochrome P450 active site containing the heme iron with six ligands. Four ligands are occupied by nitrogens from the protoporphyrin IX moiety. The fifth ligand is occupied by a sulfur from the invariant cysteine. The sixth ligand is occupied by oxygen, carbon monoxide, or water.

Ortiz de Montellano, P. R., Kunze, K. L., and Beilan, H. S. Chiral orientation of prosthetic heme in the cytochrome P450 active site. J. Biol. Chem. 258, 45-47 (1983). 

A number of theoretical calculations related to Compound I and II states and stereoselectivity of oxo-transfer reactions have been reported,and the role of the heme active site and protein environment in structure, spectra, and function of the cytochromes P450 from a theoretical point of view has been reviewed more recently. Theoretical calculations of the electron configuration of the compound I state have suggested that instead of being porphyrin-based, the radical is thiolate-based, and possible roles for a higher-spin state S = and either... 

The improvement of its activity and stability has been approach by the use of GE tools (see Refs. [398] and [399], respectively). A process drawback is the fact that the oxidation of hydrophobic compounds in an organic solvent becomes limited by substrate partition between the active site of the enzyme and the bulk solvent [398], To provide the biocatalyst soluble with a hydrophobic active site access, keeping its solubility in organic solvents, a double chemical modification on horse heart cytochrome c has been performed [400,401], First, to increase the active-site hydrophobicity, a methyl esterification on the heme propionates was performed. Then, polyethylene glycol (PEG) was used for a surface modification of the protein, yielding a protein-polymer conjugates that are soluble in organic solvents. 

Cytochrome c oxidase is an enzyme that couples the one-electron oxidation of cytochrome c to the four-electron reduction of 02 and is thus a crucial component of respiration. Cytochrome c contains the redox-active heme c, while cytochrome c oxidase contains a dinuclear Cua redox site in subunit II and three redox-active sites in subunit I heme a, heme a3, and Cur. It is believed that heme a is an electron-transfer site, while heme a3 and Cur function together at the 02 reduction site. 

He, K., Falick, A.M., Chen, B., Nilsson, F. and Correia, M.A. (1996) Identification of the heme adduct and an active site peptide modified during mechanism-based inactivation of rat liver cytochrome P450 2B1 by secobarbital. Chemical Research in Toxicology, 9 (3), 614-622. 

Figure 4 Structural details of the active site heme a3-CuB of cytochrome c oxidase...

Figure 16 X-Ray structure of the active site of cytochrome P450cam. In the camphor-bound form the bond distances are Fe-S 2.20 A Fe-N 2.05 A.33 The heme geometry of the camphor-free form is substantially similar to that of the camphor-bound form the only difference is that the iron atom is displaced from the tetrapyrrole plane towards the axial sulfur atom by 0.30 A in the camphor-free form, and by 0.44 A in the camphor-bound form...

In a very broad overview of the structural categories one can state several statistical correlations with type of function. Hemes are almost always bound by helices, but never in parallel a//3 structures. Relatively complex enzymatic functions, especially those involving allosteric control, are occasionally antiparallel /3 but most often parallel a//3. Binding and receptor proteins are most often antiparallel /3, while the proteins that bind in those receptor sites (i.e., hormones, toxins, and enzyme inhibitors) are most apt to be small disulfide-rich structures. However, there are exceptions to all of the above generalizations (such as cytochrome cs as a nonhelical heme protein or citrate synthase as a helical enzyme), and when one focuses on the really significant level of detail within the active site then the correlation with overall tertiary structure disappears altogether. For almost all of the dozen identifiable groups of functionally similar proteins that are represented by at least two known protein structures, there are at least... 

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