Cytochrome amino acid sequence

The electron transport protein, cytochrome c, found in the mitochondria of all eukaryotic organisms, provides the best-studied example of homology. The polypeptide chain of cytochrome c from most species contains slightly more than 100 amino acids and has a molecular weight of about 12.5 kD. Amino acid sequencing of cytochrome c from more than 40 different species has revealed that there are 28 positions in the polypeptide chain where the same amino acid residues are always found (Figure 5.27). These invariant residues apparently serve roles crucial to the biological function of this protein, and thus substitutions of other amino acids at these positions cannot be tolerated. 

A complete amino acid sequence for cytochrome c from N. crassa is available (81). In the case of U. sphaerogena, only an amino acid composition has been determined. U. sphaerogena forms a relatively large amount... 

Fig. 22.3 Cytochrome P450 monooxygenases and nicotine metabolism. An alignment of the amino acid sequences of the enzymes 2A6 and 2D6. Occurrences of the same amino acid residue at the same position are shown in black. Putative substrate recognition sites (SRS1—...

In the 1960, it was noticed that substitutions in some amino acid sequences seemed to occur at a roughly constant rate over time (Zuckerkandl and Pauling, 1965). This is the well known molecular clock hypothesis. For a particular protein such as cytochrome c or myoglobin, it was noticed that there was a linear relationship between divergences of pairs of sequences, as measured by numbers of amino acid differences, and divergences of the species, as measured by dates from the fossil record. There is still considerable debate as to how accurate the molecular clock may be and as to how it might vary systematically depending on the species, type of protein, and kinds of substitutions that are counted. 

The first cytochrome to be recognised as a component of the photosynthetic electron transport chain was cytochrome f [142]. The properties of cytochrome f have been reviewed [143,144], and amino-acid sequence information is available for pea, spinach, wheat and tobacco [145]. The axial ligand to the heme-Fe... 

Yasunobu, K. T., T. Nakashima, II. Higa, H. Matsubara, and A. Benson Amino acid sequence of bovi ie heart cytochrome c. Biochim. Biophys. Acta 78, 791-794 (1963). 

Matsxtbara, H., and E. L. Smith Human heart cytochrome c. Chymo-tryptic peptides, tryptic peptides and the complete amino acid sequence. Journ. Biol. Chem. 238, 2732—2753 (1963). 

Narita, K., K. Titani, Y. Yaoi, and II. Murakami The complete amino acid sequence in baker s yeast cytochrom c. Biochim. Biophys. Acta 77, 688 -690 (1963). 

Since the primary structure of a peptide determines the global fold of any protein, the amino acid sequence of a heme protein not only provides the ligands, but also establishes the heme environmental factors such as solvent and ion accessibility and local dielectric. The prevalent secondary structure element found in heme protein architectures is the a-helix however, it should be noted that p-sheet heme proteins are also known, such as the nitrophorin from Rhodnius prolixus (71) and flavocytochrome cellobiose dehydrogenase from Phanerochaete chrys-osporium (72). However, for the purpose of this review, we focus on the structures of cytochromes 6562 (73) and c (74) shown in Fig. 2, which are four-a-helix bundle protein architectures and lend themselves as resource structures for the development of de novo designs. 

Heinemann, F. S. and Ozols, J. (1983) The complete amino acid sequence of rabbit phenobarbital-induced liver microsomal cytochrome P-450. J. Biol. Chem. 258, 4195-4201. 

It was long believed that bacteria were unique in their ability to denitrify. However, Shoun and Tanimoto (1991) and Shoun et al., (1989) demonstrated that the fungus, Fusarium oxysporum, could be induced to synthesize an enzyme system capable of the anaerobic reduction of nitrite to N2O. Induction occurred under conditions of low oxygen concentrations in the presence of nitrate or nitrite. One and pethaps the only component of this nitrite reductase system is a unique, soluble cytochrome P-450 (P-450dNIR), which is more similar in its cDNA-inferred amino acid sequence to soluble, bacterial P-450 enzymes (espe-... 

The cytochrome P450 system is the principal enzyme system for the metabolism of lipophilic xenobiotics. It is a heme-containing, membrane-bound, multi-enzyme system which is present in many tissues in vivo but is present at the highest level in liver. A coenzyme, cytochrome P450 NADPH oxidoreductase (OR), is essential for P450 catalytic function and cytochrome bs may stimulate catalytic activities of some enzymes. In human liver, it is estimated that there are 15-20 different xenobiotic-metabolizing cytochrome P450 forms. A standard nomenclature, based on relatedness of the amino acid sequences, has been developed (Nelson et al., 1993). The most recent... 

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