Inhibition of the cytochrome c/cytochrome c oxidase system by cytochrome c derivatives and related fragments.
The oxidation of ferrocytochrome c mediated by cytochrome c oxidase was investigated in the presence of ferricytochrome c, trifluoroacetyl-cytochrome c, the heme fragments Hse65-[1-65] and Hse80-[1-80] and their respective porphyrin derivatives, as well as carboxymethylated apoprotein and related fragments, polycations, salts and neutral additives. The inhibition of the redox reaction by salts and neutral molecules, even if in theoretical agreement with their effect on electrostatic interactions, may alternatively be interpreted in terms of hydrophobicity. The latter can account for the inhibitory properties of trifluoroacetylated ferricytochrome c, similar to those of ferricytochrome c. On the assumption that the inhibitory properties of some of the investigated derivatives monitor their binding affinities to the cytochrome c oxidase at the cytochrome c binding sites, the experimental results do not confirm a primarily electrostatic character for the cytochrome c/cytochrome c oxidase association process. Strong indication was found that the cytochrome c C-terminal sequence is critically involved in the complex formation. Conformational studies by circular dichroism measurements and IR spectroscopy in solution and in solid state respectively, show that some of the derivatives examined may possibly acqkuire in the binding process to the oxidase, as secondary structure similar to that present in the native cytochrome c.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002942:Circular Dichroism; D003574:Cytochrome c Group / Q000378:metabolism* / Q000494:pharmacology; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors*; D006418:Heme / Q000494:pharmacology; D006736:Horses; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011487:Protein Conformation; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D000596:Amino Acids; D003574:Cytochrome c Group; D010446:Peptide Fragments; D006418:Heme; D003576:Electron Transport Complex IV