We investigate functional role of the P76GTKMIFA83 fragment of the primary structure of cytochrome c. Based on the data obtained by the analysis of informational structure (ANIS), we propose a model of functioning of cytochrome c. According to this model, conformational rearrangements of the P76GTKMIFA83 loop fragment have a significant effect on conformational mobility of the heme. It is suggested that the conformational mobility of cytochrome c heme is responsible for its optimal orientation with respect to electron donor and acceptor within ubiquinol–cytochrome c oxidoreductase (complex III) and cytochrome c oxidase (complex IV), respectively, thus, ensuring electron transfer from complex III to complex IV. To validate the model, we design several mutant variants of horse cytochrome c with multiple substitutions of amino acid residues in the P76GTKMIFA83 sequence that reduce its ability to undergo conformational rearrangements. With this, we study the succinate–cytochrome c reductase and cytochrome c oxidase activities of rat liver mitoplasts in the presence of mutant variants of cytochrome c. The electron transport activity of the mutant variants decreases to different extent. Resonance Raman spectroscopy (RRS) and surface-enhanced Raman spectroscopy (SERS) data demonstrate, that all mutant cytochromes possess heme with the higher degree of ruffling deformation, than that of the wild-type (WT) cytochrome c. The increase in the ruffled deformation of the heme of oxidized cytochromes correlated with the decrease in the electron transport rate of ubiquinol–cytochrome c reductase (complex III). Besides, all mutant cytochromes have lower mobility of the pyrrol rings and methine bridges, than WT cytochrome c. We show that a decrease in electron transport activity in the mutant variants correlates with conformational changes and reduced mobility of heme porphyrin. This points to a significant role of the P76GTKMIFA83 fragment in the electron transport function of cytochrome c.

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Several classifications of protein spatial structures and their structural elements are known. This makes revealing of the relation between these structural elements and sequence fragments rather topical. The most important move in this direction would be the determination of positional sensitivity levels and ranges between the residues in protein sequences. In this work the Shannon-Weaver informational entropy was used as a disorder criterion for solving this problem. This entropy was computed as function of the distance between the amino acid residues in different sets of unhomological protein sequences. Similarity of this function for different sets of protein sequences was shown. Analysis of informational entropy allows detecting a long-range positional correlation (> or =30) between the amino acid residues and oscillations with periods of 3.6 and 2.9. These oscillation periods correspond to periodicity of alpha- and 3(10)-helices.

The amino acid sequences of gamma-crystallin, Haloalkane Dehalogenase, Phthalate Dioxygenase, Porphobilinogen Deaminase and Myosin Regulatory Domain c-chain were analyzed for their information content. Sites of increased degree of information coordination between residues (IDIC-sites) were identified, and their organization was studied by means of analyzing the information structure of the protein sequences. Relationships between the structural units forming the spatial and informational structure of proteins were demonstrated. Associations of information-coordinated structural elements (IDIC-associations) were mapped onto compact structural domains found in the spatial structures of globular proteins. The proposed method of analyzing the information structure of protein sequences may find applications in the biotechnology and structural chemistry of proteins.

A measure of similarity between amino acid residues based on the analysis of the surroundings of each residue in primary structures of native proteins is proposed. The statistical data used for this purpose were obtained from the analysis of 168,808 protein sequences, which comprise the Protein Identification Research database (release 63). Using various threshold values of the proposed measure, amino acid residues were classified into several groups. The classification elaborated differs essentially from groupings previously used. The numerical measure of amino acid residues similarity can be used in site-directed mutagenesis studies for the prediction of probability of local spatial rearrangements in proteins.