INSTITUTO DE QUIMICA, FISICA DE LOS MATERIALES, MEDIOAMBIENTE Y ENERGIA
Unidad Ejecutora - UE
Active site structure and peroxidase activity of oxidatively modified cytochrome c species in complexes with cardiolipin
CAPDEVILA, D.A.; OVIEDO ROUCO, S.; TOMASINA, F.; TÓRTORA V.; DEMICHELI V.; RADI, R.; MURGIDA, D.H.
AMER CHEMICAL SOC
Lugar: Washington; Año: 2015 vol. 54 p. 7491 - 7491
We report a resonance Raman and UV-vis characterization of the active site structure of oxidatively modified forms of cytochrome c (Cyt-c) free in solution and in complexes with cardiolipin (CL). The studied post-translational modifications of Cyt-c include methionine sulfoxidation and tyrosine nitration, which lead to altered heme axial ligation and increased peroxidase activity with respect to the wild type protein. In spite of the structural and activity differences between the protein variants free in solution, binding to CL liposomes induces in all cases the formation of a spectroscopically identical bis-His axial coordination conformer that more efficiently promotes lipid peroxidation. The spectroscopic results indicate that the bis-His form is in equilibrium with small amounts of high spin species, thus suggesting a labile distal His ligand as the basis for the increased enzymatic activity. The protein variants nitrated in Tyr74 and sulfoxidized in Met80 present four times larger binding affinity towards CL than the unmodified Cyt-c. Based on these results, we propose that these post-translational modifications may result in amplification of the pro-apoptotic signal under oxidative stress conditions, mainly as a result of enhanced affinity towards CL rather than due to differences in the intrinsic activities of the resulting protein/CL enzymatic complexes.