Redox-active amino acids form catalytically active, one-electron oxidized radicals that occur as key intermediates in many biological electron transfer reactions. State-of-the-art quantum-mechanics/molecular-mechanics (QM/MM) and dynamical QM/MM (QM/MM MD) methods are used to characterize the electronic, vibrational, and magnetic properties of these radicals, mainly tryptophan and tyrosine radicals. In particular, we employed density functional theory and multiconfigurational perturbation methods to construct QM/MM models of i) versatile peroxidase (VP) from Pleurotus eryngii and its W164Y variant; ii) lignin peroxidase (LiP) from Phanerochaete chrysosporium, two engineered variants of LiP and Coprinus cinereus peroxidase (CiP); iii) two Pseudomonas aeruginosa azurin mutants (Az48W and ReAz108W); iv) cytochrome c peroxidase (CcP) from Saccharomyces cerevisiae. The models have been capable of reproducing specific features of their observed UV-Vis, resonance Raman, and electron paramagnetic resonance spectra. The proper modeling of the environmental effects within the QM/MM protocol, in combination with the available experimental data, has made it possible the unambiguous assignment of the experimentally detected radical species and the clarification of the nature (neutral deprotonated or cationic protonated) of the intermediates. Furthermore, a mechanistic description of the proton-coupled electron transfer process leading to the radical formation has been obtained. Additional details on the role played by the nearby protein residues and solvent water molecules in affecting the spectral properties and the geometrical structure of the radical intermediates have also been provided. Indeed, the computational models are able to correctly replicate the spectral changes imposed by the eventually contrasting hydrophobic and hydrophilic environments in which the radicals are embedded. Most importantly, the same models have proven useful to disentangle the molecular-level interactions responsible for such changes. The results obtained are expected to shed new light on the catalytic mechanism involving radical species and thus open the way to a comprehensive understanding of radical-mediated ET reactions.

Bernini, C., Arezzini, E., Pogni, R., Olivucci, M., Basosi, R., Sinicropi, A. (2013). Triptophan and Tyrosine radicals mediating ET processes in peroxidases and blue copper proteins. In ET4HEALTH 2013 (pp.53-53).

Triptophan and Tyrosine radicals mediating ET processes in peroxidases and blue copper proteins

Pogni R.;OLIVUCCI, MASSIMO;BASOSI, RICCARDO;SINICROPI, ADALGISA
2013-01-01

Abstract

Redox-active amino acids form catalytically active, one-electron oxidized radicals that occur as key intermediates in many biological electron transfer reactions. State-of-the-art quantum-mechanics/molecular-mechanics (QM/MM) and dynamical QM/MM (QM/MM MD) methods are used to characterize the electronic, vibrational, and magnetic properties of these radicals, mainly tryptophan and tyrosine radicals. In particular, we employed density functional theory and multiconfigurational perturbation methods to construct QM/MM models of i) versatile peroxidase (VP) from Pleurotus eryngii and its W164Y variant; ii) lignin peroxidase (LiP) from Phanerochaete chrysosporium, two engineered variants of LiP and Coprinus cinereus peroxidase (CiP); iii) two Pseudomonas aeruginosa azurin mutants (Az48W and ReAz108W); iv) cytochrome c peroxidase (CcP) from Saccharomyces cerevisiae. The models have been capable of reproducing specific features of their observed UV-Vis, resonance Raman, and electron paramagnetic resonance spectra. The proper modeling of the environmental effects within the QM/MM protocol, in combination with the available experimental data, has made it possible the unambiguous assignment of the experimentally detected radical species and the clarification of the nature (neutral deprotonated or cationic protonated) of the intermediates. Furthermore, a mechanistic description of the proton-coupled electron transfer process leading to the radical formation has been obtained. Additional details on the role played by the nearby protein residues and solvent water molecules in affecting the spectral properties and the geometrical structure of the radical intermediates have also been provided. Indeed, the computational models are able to correctly replicate the spectral changes imposed by the eventually contrasting hydrophobic and hydrophilic environments in which the radicals are embedded. Most importantly, the same models have proven useful to disentangle the molecular-level interactions responsible for such changes. The results obtained are expected to shed new light on the catalytic mechanism involving radical species and thus open the way to a comprehensive understanding of radical-mediated ET reactions.
2013
Bernini, C., Arezzini, E., Pogni, R., Olivucci, M., Basosi, R., Sinicropi, A. (2013). Triptophan and Tyrosine radicals mediating ET processes in peroxidases and blue copper proteins. In ET4HEALTH 2013 (pp.53-53).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/726329
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