| dc.description | Cytochrome c is a small heme-containing protein, found in the intermembrane space of mitochondria, which forms a key link in the process of oxidative phosphorylation by transferring electrons between Complexes III and IV, in addition to a number of other mitochondrial electron-transport proteins. Studies of this critical protein are aimed at elucidating the nature of electron transport, intermolecular interactions, and protein folding and structure. In the first part of this work, a number of mutants of S. cerevisiae iso-1 cytochrome c have been examined involving mutations of two surface charged residues, Arg13 and Asp90, and two partially buried residues, Phe82 and Leu85. Modifications of Arg13 leads to major deviations in electron transport while those of Asp90 lead to more structural effects. For the two hydrophobic residues, structural disruptions appear to be related to the size of residue 85 while functional disruptions are related to the hydrophobicity, suggesting that conservation of this residue maintains aspects of both. In the second part, a binding model of ATP to horse cytochrome c has been developed using a computer simulation with energy minimisation, and suggests that the nucleotide binds to the protein surface proximal to the invariant Arg91, a number of lysine residues, and Glu69. In the third part of this study, computer modelling of a number of "methionine scan" mutants of S. cerevisiae iso-1 cytochrome c was carried out to complement a number of structural and functional studies. The results show that methionine insertions can be tolerated in many different locations but may have unexpected effects based on the evolutionary variability of an amino acid, as replacement of the variable Lys55 apparently leads to structural and functional disruptions. | en_US |
