Protein Oxidation of Cytochrome c by Reactive Halogen Species Enhances Its Peroxidase Activity

Chen, Yeong‐Renn; Deterding, Leesa J.; Sturgeon, Bradley E.; Tomer, Kenneth B.; Mason, Ronald P.

doi:10.1074/jbc.m200709200

Cited by 106 publications

(143 citation statements)

References 58 publications

Supporting

Mentioning

133

Contrasting

Order By: Relevance

“…The hexacoordinate organization of heme-iron, however, hinders binding and chemical interactions of cyt c with small molecules such as NO, O 2 , CO, and H 2 O 2 ; therefore cyt c in solution exhibits only a marginal peroxidase activity (2)(3)(4)(5)(6). The hindrance can be eliminated, and the redox catalytic reactivity can be conferred on cyt c by converting its hexa-coordinate arrangement into a penta-coordinate form by full or partial unfolding of the protein with strong denaturing agents such as guanidine chloride or chemical modification of Met 80 (7,8). Similar structural perturbations accompanied by an exchange and a loss of axial ligands and an increase of peroxidase activity were observed when cyt c interacted with negatively charged phospholipid membranes (3-5, 9 -11).…”

Section: Cyt Cmentioning

confidence: 99%

Nitric Oxide Inhibits Peroxidase Activity of Cytochrome c· Cardiolipin Complex and Blocks Cardiolipin Oxidation

Vlasova

Tyurin

Kapralov

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

The increased production of NO during the early stages of apoptosis indicates its potential involvement in the regulation of programmed cell death through yet to be identified mechanisms. Recently, an important role for catalytically competent peroxidase form of pentacoordinate cytochrome c (cyt c) in a complex with a mitochondriaspecific phospholipid, cardiolipin (CL), has been demonstrated during execution of the apoptotic program. Because the cyt c⅐CL complex acts as CL oxygenase and selectively oxidizes CL in apoptotic cells in a reaction dependent on the generation of protein-derived (tyrosyl) radicals, we hypothesized that binding and nitrosylation of cyt c regulates CL oxidation. Here we demonstrate by low temperature electron paramagnetic resonance spectroscopy that CL facilitated interactions of ferro-and ferri-states of cyt c with NO and NO ؊ , respectively, to yield a mixture of penta-and hexa-coordinate nitrosylated cyt c. In the nitrosylated cyt c⅐CL complex, NO chemically reacted with H 2 O 2 -activated peroxidase intermediates resulting in their reduction. A dose-dependent quenching of H 2 O 2 -induced protein-derived radicals by NO donors was shown using direct electron paramagnetic resonance measurements as well as immuno-spin trapping with antibodies against protein 5,5-dimethyl-1-pyrroline N-oxide-nitrone adducts. In the presence of NO donors, H 2 O 2 -induced oligomeric forms of cyt c positively stained for 3-nitrotyrosine confirming the reactivity of NO toward tyrosyl radicals of cyt c. Interaction of NO with the cyt c⅐CL complex inhibited its peroxidase activity with three different substrates: CL, etoposide, and 3,3-diaminobenzidine. Given the importance of CL oxidation in apoptosis, mass spectrometry analysis was utilized to assess the effects of NO on oxidation of 1,12,2-tertalinoleoyl cardiolipin. NO effectively inhibited 1,12,2-tertalinoleoyl cardiolipin oxidation catalyzed by the peroxidase activity of cyt c. Thus, NO can act as a regulator of peroxidase activity of cyt c⅐CL complexes.

show abstract

Section: Cyt Cmentioning

confidence: 99%

Nitric Oxide Inhibits Peroxidase Activity of Cytochrome c· Cardiolipin Complex and Blocks Cardiolipin Oxidation

Vlasova

Tyurin

Kapralov

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…CL-bound cytc shows a non-native tertiary structure, a disrupted heme-Fe-Met80 distal bond [12][13][14][15][16][17], and a drastically reduced midpoint potential, which falls out of the range required for its physiological role [18]. Further, the cleavage of the distal Fe-Met80 bond endows cytc with a high affinity for CO and NO [19,20] and peroxidase activity [21][22][23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Cardiolipin modulates allosterically peroxynitrite detoxification by horse heart cytochrome c

Ascenzi

Ciaccio

Sinibaldi

et al. 2011

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

a b s t r a c tUpon interaction with bovine heart cardiolipin (CL), horse heart cytochrome c (cytc) changes its tertiary structure disrupting the heme-Fe-Met80 distal bond, reduces drastically the midpoint potential out of the range required for its physiological role, binds CO and NO with high affinity, and displays peroxidase activity. Here, the effect of CL on peroxynitrite isomerization by ferric cytc (cytc-Fe(III)) is reported. In the absence of CL, hexa-coordinated cytc does not catalyze peroxynitrite isomerization. In contrast, CL facilitates cytc-Fe(III)-mediated isomerization of peroxynitrite in a dose-dependent fashion inducing the penta-coordination of the heme-Fe(III)-atom. The value of the second order rate constant for CLcytc-Fe(III)-mediated isomerization of peroxynitrite (k on ) is (3.2 ± 0.4) Â 10 5 M À1 s À1. The apparent dissociation equilibrium constant for CL binding to cytc-Fe(III) is (5.1 ± 0.8) Â 10 À5 M. These results suggest that CL-cytc could play either pro-apoptotic or anti-apoptotic effects facilitating lipid peroxidation and scavenging of reactive nitrogen species, such as peroxynitrite, respectively.

show abstract

“…Amino acid analysis of Cyt-c following visible light irradiation of a hematoporphyrin solution resulted in destruction of His, Trp, Tyr, and Met residues [19]. Direct evidence for modification of amino acid side chains of Cyt-c or other mitochondrial proteins by 1 O 2 has not been reported to our knowledge [35]; however, the chemical modification of Cyt-c attendant to various forms of oxidative stress has been well studied [36][37][38][39][40].…”

Section: Role Of Cytochrome-c In Response To 1 Omentioning

confidence: 99%

“…Modification of His26 can be detected only when the trypsin cleavage at Lys27 is missed, with the resulting peptide containing both His26 and His33 (K 25 .HKTGPNLHGLFGK 38 ). In every MALDI-TOF spectrum of peptides obtained following exposure of Cyt-c to 1 O 2 , the HKTGPNLHGLFGK +32 Da peptide was always the most intense modified peptide, and sometimes the only one observed.…”

Section: Characterization Of His Modificationsmentioning

confidence: 99%

Oxidative modification of cytochrome c by singlet oxygen

Kim¹,

Rodriguez²,

Guo³

et al. 2008

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Singlet oxygen ( 1 O 2 ) is a reactive oxygen species that may be generated in biological systems. Photodynamic therapy generates 1 O 2 by photoexcitation of sensitizers resulting in intracellular oxidative stress and induction of apoptosis. 1 O 2 oxidizes amino acid side chains of proteins and inactivates enzymes when generated in vitro. Among proteogenic amino acids, His, Tyr, Met, Cys, and Trp are known to be oxidized by 1 O 2 at physiological pH. However, there is a lack of direct evidence of oxidation of proteins by 1 O 2 . Because 1 O 2 is difficult to detect in cells, identifying oxidized cellular products uniquely derived from 1 O 2 could serve as a marker of its presence. In the present study, 1 O 2 reactions with model peptides analyzed by tandem mass spectrometry provide insight into the mass of prominent adducts formed with the reactive amino acids. Analysis by MALDI-TOF and tandem mass spectrometry of peptides of cytochrome c exposed to 1 O 2 generated by photoexcitation of the phthalocyanine Pc 4 showed unique oxidation products, which might be used as markers of the presence of 1 O 2 in the mitochondrial intermembrane space. Differences in the elemental composition of the oxidized amino acid residues observed with cytochrome c and the model peptides suggest the protein environment can affect the oxidation pathway.

show abstract

Protein Oxidation of Cytochrome c by Reactive Halogen Species Enhances Its Peroxidase Activity

Cited by 106 publications

References 58 publications

Nitric Oxide Inhibits Peroxidase Activity of Cytochrome c· Cardiolipin Complex and Blocks Cardiolipin Oxidation

Nitric Oxide Inhibits Peroxidase Activity of Cytochrome c· Cardiolipin Complex and Blocks Cardiolipin Oxidation

Cardiolipin modulates allosterically peroxynitrite detoxification by horse heart cytochrome c

Oxidative modification of cytochrome c by singlet oxygen

Contact Info

Product

Resources

About