Peroxidase activity of cytochrome c in its compact state depends on dynamics of the heme region

Nataša Tomášková, Rastislav Varhač, Veronika Lysáková, Andrej Musatov, Erik Sedlák

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Cytochrome c (cyt c) is a small globular hemoprotein with the main function as an electron carrier in mitochondrial respiratory chain. Cyt c possesses also peroxidase-like activity in the native state despite its six-coordinated heme iron. In this work, we studied the effect of increasing urea concentration in the range from 0 M to 6 M at pH 7 (pH value of the bulk solvent) and pH 5 (pH value close to negatively charged membrane) on peroxidase-like activity of cyt c. We show that peroxidase-like activity, measured by guaiacol oxidation and the ferrous oxidation in xylenol orange methods, correlates with the accessibility of the heme iron, which was assessed from the association rate constant of cyanide binding to cyt c. Cyt c peroxidase-like activity linearly increases in the pre-denaturational urea concentrations (0–4 M) at both studied pHs without an apparent formation of penta-coordinated state of the heme iron. Our results suggest that dynamic equilibrium among the denaturant-induced non-native coordination states of cyt c, very likely due to reversible unfolding of the least stable foldons, is pre-requisite for enhanced peroxidase-like activity of cyt c in its compact state. Dynamic replacement of the native sixth coordination bond of methionine-80 by lysines (72, 73, and 79) and partially also by histidines (26 and 33) provides an efficient way how to increase peroxidase-like activity of cyt c without significant conformational change at physiological conditions.

Original languageEnglish (US)
Pages (from-to)1073-1083
Number of pages11
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Issue number11
StatePublished - Nov 2018
Externally publishedYes


  • Accessibility of heme iron
  • Cytochrome c
  • Foldons
  • Heme region dynamics
  • Peroxidase-like activity

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology


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