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The hierarchy of structural transitions induced in cytochrome c by anionic phospholipids determines its peroxidase activation and selective peroxidation during apoptosis in cells.

Authors
Kapralov-AA; Kurnikov-IV; Vlasova-II; Belikova-NA; Tyurin-VA; Basova-LV; Zhao-Q; Tyurina-YY; Jiang-J; Bayir-H; Vladimirov-YA; Kagan-VE
Source
Biochemistry 2007 Dec; 46(49):14232-14244
NIOSHTIC No.
20033313
Abstract
Activation of peroxidase catalytic function of cytochrome c (cyt c) by anionic lipids is associated with destabilization of its tertiary structure. We studied effects of several anionic phospholipids on the protein structure by monitoring (1) Trp59 fluorescence, (2) Fe-S(Met80) absorbance at 695 nm, and (3) EPR of heme nitrosylation. Peroxidase activity was probed using several substrates and protein-derived radicals. Peroxidase activation of cyt c did not require complete protein unfolding or breakage of the Fe-S(Met80) bond. The activation energy of cyt c peroxidase changed in parallel with stability energies of structural regions of the protein probed spectroscopically. Cardiolipin (CL) and phosphatidic acid (PA) were most effective in inducing cyt c peroxidase activity. Phosphatidylserine (PS) and phosphatidylinositol bisphosphate (PIP2) displayed a significant but much weaker capacity to destabilize the protein and induce peroxidase activity. Phosphatidylinositol trisphosphate (PIP3) appeared to be a stronger inducer of cyt c structural changes than PIP2, indicating a role for the negatively charged extra phosphate group. Comparison of cyt c-deficient HeLa cells and mouse embryonic cells with those expressing a full complement of cyt c demonstrated the involvement of cyt c peroxidase activity in selective catalysis of peroxidation of CL, PS, and PI, which corresponded to the potency of these lipids in inducing cyt c's structural destabilization.
Keywords
Metabolism; Cell-metabolism; Enzymes; Enzyme-activity; Lipids; Lipid-peroxidation; Oxidation-reduction-reactions; Oxidation; Cellular-transport-mechanism; Cellular-structures
Contact
Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260
CODEN
BICHAW
Publication Date
20071211
Document Type
Journal Article
Funding Type
Grant
Fiscal Year
2008
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-008282
Issue of Publication
49
ISSN
0006-2960
Source Name
Biochemistry
State
PA
Performing Organization
University of Pittsburgh at Pittsburgh
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