ArticleThe Journal of biological chemistry2009
Nitration of solvent-exposed tyrosine 74 on cytochrome c triggers heme iron-methionine 80 bond disruption. Nuclear magnetic resonance and optical spectroscopy studies.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 99 citations in OpenAlex.
- Nitration-driven structural changes in Hsp90 linked to gain of pathological functions.The Biochemical journal · 2025Article
- De novo sequencing and construction of a unique antibody for the recognition of alternative conformations of cytochromeProceedings of the National Academy of Sciences of the United States of America · 2022Article
- New insights into the folding-unfolding mechanism and conformations of cytochrome C.Chemical science · 2022Article
- Post-Translational Modifications of CytochromeInternational journal of molecular sciences · 2020Review
- Wheel and Deal in the Mitochondrial Inner Membranes: The Tale of CytochromeOxidative medicine and cellular longevity · 2020Review
- Exploring protein phosphorylation by combining computational approaches and biochemical methods.Computational and structural biotechnology journal · 2020Article
- Lysine carbonylation is a previously unrecognized contributor to peroxidase activation of cytochromeChemical science · 2019Article
- Tissue-specific regulation of cytochrome c by post-translational modifications: respiration, the mitochondrial membrane potential, ROS, and apoptosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Review
- Fundamentals on the biochemistry of peroxynitrite and protein tyrosine nitration.Redox biology · 2018Review
- Nitroso-Oxidative Stress, Acute Phase Response, and Cytogenetic Damage in Wistar Rats Treated with Adrenaline.Oxidative medicine and cellular longevity · 2018Article
- Interplay between oxidant species and energy metabolism.Redox biology · 2016Review
- Sulfite Oxidase Activity of Cytochrome c: Role of Hydrogen Peroxide.Biochemistry and biophysics reports · 2016Article
- Mitochondrial oxidative metabolism and uncoupling proteins in the failing heart.Heart failure reviews · 2015Review
- Tyrosine nitration as mediator of cell death.Cellular and molecular life sciences : CMLS · 2014Review
- Cardiolipin modulates allosterically the nitrite reductase activity of horse heart cytochrome c.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2014Article
- Structural and molecular basis of the peroxynitrite-mediated nitration and inactivation of Trypanosoma cruzi iron-superoxide dismutases (Fe-SODs) A and B: disparate susceptibilities due to the repair of Tyr35 radical by Cys83 in Fe-SODB through intramolecular electron transfer.The Journal of biological chemistry · 2014Article
- Evaluation of a method for nitrotyrosine site identification and relative quantitation using a stable isotope-labeled nitrated spike-in standard and high resolution fourier transform MS and MS/MS analysis.International journal of molecular sciences · 2014Article
- The role of key residues in structure, function, and stability of cytochrome-c.Cellular and molecular life sciences : CMLS · 2014Review
- Peroxynitrite, a stealthy biological oxidant.The Journal of biological chemistry · 2013Review
- Regulation of the intrinsic apoptosis pathway by reactive oxygen species.Antioxidants & redox signaling · 2013Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Cytochrome c, a mitochondrial electron transfer protein containing a hexacoordinated heme, is involved in other physiologically relevant events, such as the triggering of apoptosis, and the activation of a peroxidatic activity. The latter occurs secondary to interactions with cardiolipin and/or post-translational modifications, including tyrosine nitration by peroxynitrite and other nitric oxide-derived oxidants. The gain of peroxidatic activity in nitrated cytochrome c has been related to a heme site transition in the physiological pH region, which normally occurs at alkaline pH in the native protein. Herein, we report a spectroscopic characterization of two nitrated variants of horse heart cytochrome c by using optical spectroscopy studies and NMR. Highly pure nitrated cytochrome c species modified at solvent-exposed Tyr-74 or Tyr-97 were generated after treatment with a flux of peroxynitrite, separated, purified by preparative high pressure liquid chromatography, and characterized by mass spectrometry-based peptide mapping. It is shown that nitration of Tyr-74 elicits an early alkaline transition with a pKa = 7.2, resulting in the displacement of the sixth and axial iron ligand Met-80 and replacement by a weaker Lys ligand to yield an alternative low spin conformation. Based on the study of site-specific Tyr to Phe mutants in the four conserved Tyr residues, we also show that this transition is not due to deprotonation of nitro-Tyr-74, but instead we propose a destabilizing steric effect of the nitro group in the mobile Omega-loop of cytochrome c, which is transmitted to the iron center via the nearby Tyr-67. The key role of Tyr-67 in promoting the transition through interactions with Met-80 was further substantiated in the Y67F mutant. These results therefore provide new insights into how a remote post-translational modification in cytochrome c such as tyrosine nitration triggers profound structural changes in the heme ligation and microenvironment and impacts in protein function.
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