title: In silico spectroscopy of tryptophan and tyrosine radicals involved in the long-range electron transfer of cytochrome c peroxidase.
abstract: Cytochrome c peroxidase (CcP) is a heme-containing enzyme that catalyzes the oxidation of the ferrocytochrome c to ferricytochrome c with concomitant reduction of H2O2 to H2O. Its catalytic cycle involves the formation of a double oxidized species (compound I) consisting of an oxoferryl center (Fe(IV)═O) and an amino acid radical (R(•)). Here we use a quantum-mechanics/molecular-mechanics (QM/MM) computational protocol based on density functional theory (DFT) and multiconfigurational perturbation theory (CASPT2) methods to reproduce specific features of compound I EPR and UV-vis spectra. The results show that the employed QM/MM models can correctly predict the magnetic, electronic and vibrational properties of the observed amino acid radicals of compound I. Furthermore, we have been able to confirm that the principal radical species of compound I is a tryptophan cationic radical located on residue 191 (Trp191(•+)) and that three tyrosine residues (Tyr203, Tyr236, and Tyr251), located along two possible ET pathways involving Trp191(•+), are possible candidates to host the secondary radical species.
authors.affiliation: Department of Biotechnology, Chemistry and Pharmacy, University of Siena , Via A. Moro 2, 53100 Siena, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Bernini
authors.forename: Elena
authors.initials: E
authors.lastname: Arezzini
authors.forename: Riccardo
authors.initials: R
authors.lastname: Basosi
authors.forename: Adalgisa
authors.initials: A
authors.lastname: Sinicropi
mesh_terms: D003578:Cytochrome-c Peroxidase / Q000737:chemistry* / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D004579:Electron Transport; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D011789:Quantum Theory; D014364:Tryptophan / Q000737:chemistry* / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry* / Q000378:metabolism
chemical_list: D005609:Free Radicals; D014443:Tyrosine; D014364:Tryptophan; D003578:Cytochrome-c Peroxidase