Mechanism of activation of cytochrome c peroxidase activity by cardiolipin |
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Authors: | Yu. A. Vladimirov E. V. Proskurnina D. Yu. Izmailov A. A. Novikov A. V. Brusnichkin A. N. Osipov V. E. Kagan |
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Affiliation: | (1) Faculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovskii pr. 31/5, 117192 Moscow, Russia;(2) Russian State Medical University, ul. Ostrovityanova 1, 117997 Moscow, Russia;(3) Faculty of Chemistry, Lomonosov Moscow State University, 119992 Moscow, Russia;(4) University of Pittsburgh, 100 Technology Dr., Suite 333, Pittsburgh, PA 15260, USA |
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Abstract: | In this work, the actions of bovine heart cardiolipin, synthetic tetraoleyl cardiolipin, and a nonspecific anionic detergent sodium dodecyl sulfate (SDS) on cytochrome c (Cyt c) peroxidase activity recorded by chemiluminescence in the presence of luminol and on the Fe...S(Met80) bond whose presence was estimated by a weak absorption band amplitude with peak at 695-700 nm (A(695)) were compared. A strict concurrency between Fe...S(Met80) breaking (A(695)) and cytochrome peroxidase activity enhancement was shown to exist at cardiolipin/Cyt c and SDS/Cyt c molar ratios of 0 : 1 to 50 : 1 (by chemiluminescence). Nevertheless, when A(695) completely disappeared, Cyt c peroxidase activity under the action of cardiolipin was 20 times more than that under the action of SDS, and at low ligand/protein molar ratios (=4), SDS failed to activate peroxidase activity while cardiolipin enhanced Cyt c peroxidase activity 16-20-fold. A(695) did not change on Cyt c binding with liposomes consisting of tetraoleyl cardiolipin and phosphatidylcholine (1 : 10 : 10), while peroxidase activity was enhanced by a factor of 8. Breaking of 70% of the Fe...S(Met80) bonds resulted in only threefold enhancement of peroxidase activity. Cardiolipin-activated Cyt c peroxidase activity was reduced by high ionic strength solution (1 M KCl). The aggregated data suggest that cardiolipin activating action is caused, first, by a nonspecific effect of Fe...S(Met80) breaking as the result of conformational changes in the protein globule caused by the protein surface electrostatic recharging by an anionic amphiphilic molecule, and second, by a specific acceleration of the peroxidation reaction which is most likely due to enhanced heme accessibility for H(2)O(2) as a result of the hydrophobic interaction between cardiolipin and cytochrome. |
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Keywords: | cytochrome c cardiolipin peroxidase activity |
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