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Ligand accessibility to heme cytochrome b5 coordinating sphere and enzymatic activity enhancement upon tyrosine ionization

Authors
  • Samhan-Arias, Alejandro K.1
  • Cordas, Cristina M.1
  • Carepo, Marta S.1
  • Maia, Luisa B.1
  • Gutierrez-Merino, Carlos2
  • Moura, Isabel1
  • Moura, José J. G.1
  • 1 Universidade Nova de Lisboa, LAQV, REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Lisbon, 2829-516, Portugal , Lisbon (Portugal)
  • 2 University of Extremadura, Department of Biochemistry and Molecular Biology, Faculty of Sciences and Institute of Molecular Pathology Biomarkers, Badajoz, 06006, Spain , Badajoz (Spain)
Type
Published Article
Journal
JBIC Journal of Biological Inorganic Chemistry
Publisher
Springer-Verlag
Publication Date
Mar 05, 2019
Volume
24
Issue
3
Pages
317–330
Identifiers
DOI: 10.1007/s00775-019-01649-2
Source
Springer Nature
Keywords
License
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Abstract

Recently, we observed that at extreme alkaline pH, cytochrome b5 (Cb5) acquires a peroxidase-like activity upon formation of a low spin hemichrome associated with a non-native state. A functional characterization of Cb5, in a wide pH range, shows that oxygenase/peroxidase activities are stimulated in alkaline media, and a correlation between tyrosine ionization and the attained enzymatic activities was noticed, associated with an altered heme spin state, when compared to acidic pH values at which the heme group is released. In these conditions, a competitive assay between imidazole binding and Cb5 endogenous heme ligands revealed the appearance of a binding site for this exogenous ligand that promotes a heme group exposure to the solvent upon ligation. Our results shed light on the mechanism behind Cb5 oxygenase/peroxidase activity stimulation in alkaline media and reveal a role of tyrosinate anion enhancing Cb5 enzymatic activities on the distorted protein before maximum protein unfolding.

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