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Capdevila 2015 Biochemistry

From Bioblast
Publications in the MiPMap
Capdevila DA, Oviedo Rouco S, Tomasina F, Tortora V, Demicheli V, Radi R, Murgida DH (2015) Active site structure and peroxidase activity of oxidatively modified cytochrome c species in complexes with cardiolipin. Biochemistry 54:7491-504.

Β» PMID: 26620444

Capdevila DA, Oviedo Rouco S, Tomasina F, Tortora V, Demicheli V, Radi R, Murgida DH (2015) Biochemistry

Abstract: 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 those of 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 CL-induced increase in enzymatic activity observed for all protein variants. For Cyt-c nitrated at Tyr74 and sulfoxidized at Met80, the measured apparent binding affinities for CL are ∼4 times larger than for wild-type Cyt-c. On the basis of these results, we propose that these post-translational modifications may amplify the pro-apoptotic signal of Cyt-c under oxidative stress conditions at CL concentrations lower than for the unmodified protein. β€’ Keywords: Amplex Red, Cytochrome c, Liposome

β€’ O2k-Network Lab: UY Montevideo Radi R


Labels: MiParea: Respiration, Genetic knockout;overexpression 


Tissue;cell: Fat 


Regulation: Cyt c 


HRR: Oxygraph-2k 

2016-01