Topography of tyrosine residues and their involvement in peroxidation of polyunsaturated cardiolipin in cytochrome c/cardiolipin peroxidase complexes

Details

• Personal Author:
  Castro L ; Demicheli V ; Kagan VE ; Kapralov AA ; Klein-Seetharaman J ; Maeda A ; Mylnikov D ; Peterson J ; Radi R ; Samhan-Arias A ; Tortora V ; Tyurina YY ; Vladimirov YA ; Weitz AA ; Yanamala N
• Description:
  Formation of cytochrome c (cyt c)/cardiolipin (CL) peroxidase complex selective toward peroxidation of polyunsaturated CLs is a pre-requisite for mitochondrial membrane permeabilization. Tyrosine residues - via the generation of tyrosyl radicals (Tyr) - are likely reactive intermediates of the peroxidase cycle leading to CL peroxidation. We used mutants of horse heart cyt c in which each of the four Tyr residues was substituted for Phe and assessed their contribution to the peroxidase catalysis. Tyr67Phe mutation was associated with a partial loss of the oxygenase function of the cyt c/CL complex and the lowest concentration of H(2)O(2)-induced Tyr radicals in electron paramagnetic resonance (EPR) spectra. Our MS experiments directly demonstrated decreased production of CL-hydroperoxides (CL-OOH) by Tyr67Phe mutant. Similarly, oxidation of a phenolic substrate, Amplex Red, was affected to a greater extent in Tyr67Phe than in three other mutants. Tyr67Phe mutant exerted high resistance to H(2)O(2)-induced oligomerization. Measurements of Tyr fluorescence, hetero-nuclear magnetic resonance (NMR) and computer simulations position Tyr67 in close proximity to the porphyrin ring heme iron and one of the two axial heme-iron ligand residues, Met80. Thus, the highly conserved Tyr67 is a likely electron-donor (radical acceptor) in the oxygenase half-reaction of the cyt c/CL peroxidase complex. [Description provided by NIOSH]
• Subjects:
  Animals Cytology Energy Metabolism Ferrous Compounds Free Radicals Histocytochemistry Occupational Health Safety
• Keywords:
  Author Keywords: Cytochrome C Cardiolipin Cardiolipin Hydroperoxide Cell-alteration Cell-function Cell-metabolism Cytochemistry Free-radical-generation Free-radicals Heart Hydroperoxides Iron-compounds Membrane-filters Metabolism Mutation Myocardium Oxidation Oxidative-processes Peroxidase Peroxidases Phenyls Simulation-methods Spectroscopes Tyrosine

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• ISSN:
  0006-3002
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  1808
• Issue:
  9
• NIOSHTIC Number:
  nn:20039648
• Citation:
  Biochim Biophys Acta 2011 Sep; 1808(9):2147-2155
• Contact Point Address:
  Valerian E. Kagan, Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Bridgeside Point 100 Technology Drive, Suite 350, Pittsburgh, PA, USA
• CAS Registry Number:
  Hydrogen peroxide (CAS RN 7722-84-1) ; Iron (CAS RN 7439-89-6) ; L-Tyrosine (CAS RN 55520-40-6) ; Oxygen (CAS RN 7782-44-7)
• Federal Fiscal Year:
  2011
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Biochimica et Biophysica Acta
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:82dd85a5a836a4516e2b22c31e541308d2fbe12d277eacafed36e82f38c3ff134cf68b605578de9732301b3346f77d14674b93fc989d8e3d4988f6c6222302a5
• Download URL:
  https://stacks.cdc.gov/view/cdc/192815/cdc_192815_DS1.pdf
• File Type:
  [PDF - 1.28 MB ]