Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution

Experimental studies in hemeproteins and model Tyr/Cys-containing peptides exposed to oxidizing and nitrating species suggest that intramolecular electron transfer (IET) between tyrosyl radicals (Tyr-O) and Cys residues controls oxidative modification yields. The molecular basis of this IET process...

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Autores principales:	Petruk, Ariel Alcides, Estrin, Dario Ariel, Murgida, Daniel Horacio, Martí, Marcelo Adrián
Publicado:	2012
Materias:	Computer simulation Electron transfer Nitration Oxidation Tyrosyl radical alanine cysteine hydrogen phenol derivative thiol derivative tyrosine water acid base balance amino acid sequence article chemical reaction kinetics chemical structure computer simulation electron transport hydrogen bond molecular dynamics oxidation physical chemistry priority journal protein conformation protein modification protein structure proton transport quantum mechanics solvation thermodynamics Computer Simulation Cysteine Electron Transport Free Radicals Kinetics Molecular Dynamics Simulation Peptides Proteins Quantum Theory Solutions Tyrosine Water
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00039861_v525_n1_p82_Petruk http://hdl.handle.net/20.500.12110/paper_00039861_v525_n1_p82_Petruk
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_00039861_v525_n1_p82_Petruk
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spelling	paper:paper_00039861_v525_n1_p82_Petruk2023-06-08T14:25:06Z Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution Petruk, Ariel Alcides Estrin, Dario Ariel Murgida, Daniel Horacio Martí, Marcelo Adrián Computer simulation Electron transfer Nitration Oxidation Tyrosyl radical alanine cysteine hydrogen phenol derivative thiol derivative tyrosine water acid base balance amino acid sequence article chemical reaction kinetics chemical structure computer simulation electron transport hydrogen bond molecular dynamics oxidation physical chemistry priority journal protein conformation protein modification protein structure proton transport quantum mechanics solvation thermodynamics Computer Simulation Cysteine Electron Transport Free Radicals Kinetics Molecular Dynamics Simulation Peptides Proteins Quantum Theory Solutions Tyrosine Water Experimental studies in hemeproteins and model Tyr/Cys-containing peptides exposed to oxidizing and nitrating species suggest that intramolecular electron transfer (IET) between tyrosyl radicals (Tyr-O) and Cys residues controls oxidative modification yields. The molecular basis of this IET process is not sufficiently understood with structural atomic detail. Herein, we analyzed using molecular dynamics and quantum mechanics-based computational calculations, mechanistic possibilities for the radical transfer reaction in Tyr/Cys-containing peptides in solution and correlated them with existing experimental data. Our results support that Tyr-O to Cys radical transfer is mediated by an acid/base equilibrium that involves deprotonation of Cys to form the thiolate, followed by a likely rate-limiting transfer process to yield cysteinyl radical and a Tyr phenolate; proton uptake by Tyr completes the reaction. Both, the pKa values of the Tyr phenol and Cys thiol groups and the energetic and kinetics of the reversible IET are revealed as key physico-chemical factors. The proposed mechanism constitutes a case of sequential, acid/base equilibrium-dependent and solvent-mediated, proton-coupled electron transfer and explains the dependency of oxidative yields in Tyr/Cys peptides as a function of the number of alanine spacers. These findings contribute to explain oxidative modifications in proteins that contain sequence and/or spatially close Tyr-Cys residues. © 2012 Elsevier Inc. All rights reserved. Fil:Petruk, A.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Estrin, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Murgida, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Marti, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2012 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00039861_v525_n1_p82_Petruk http://hdl.handle.net/20.500.12110/paper_00039861_v525_n1_p82_Petruk
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Computer simulation Electron transfer Nitration Oxidation Tyrosyl radical alanine cysteine hydrogen phenol derivative thiol derivative tyrosine water acid base balance amino acid sequence article chemical reaction kinetics chemical structure computer simulation electron transport hydrogen bond molecular dynamics oxidation physical chemistry priority journal protein conformation protein modification protein structure proton transport quantum mechanics solvation thermodynamics Computer Simulation Cysteine Electron Transport Free Radicals Kinetics Molecular Dynamics Simulation Peptides Proteins Quantum Theory Solutions Tyrosine Water
spellingShingle	Computer simulation Electron transfer Nitration Oxidation Tyrosyl radical alanine cysteine hydrogen phenol derivative thiol derivative tyrosine water acid base balance amino acid sequence article chemical reaction kinetics chemical structure computer simulation electron transport hydrogen bond molecular dynamics oxidation physical chemistry priority journal protein conformation protein modification protein structure proton transport quantum mechanics solvation thermodynamics Computer Simulation Cysteine Electron Transport Free Radicals Kinetics Molecular Dynamics Simulation Peptides Proteins Quantum Theory Solutions Tyrosine Water Petruk, Ariel Alcides Estrin, Dario Ariel Murgida, Daniel Horacio Martí, Marcelo Adrián Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution
topic_facet	Computer simulation Electron transfer Nitration Oxidation Tyrosyl radical alanine cysteine hydrogen phenol derivative thiol derivative tyrosine water acid base balance amino acid sequence article chemical reaction kinetics chemical structure computer simulation electron transport hydrogen bond molecular dynamics oxidation physical chemistry priority journal protein conformation protein modification protein structure proton transport quantum mechanics solvation thermodynamics Computer Simulation Cysteine Electron Transport Free Radicals Kinetics Molecular Dynamics Simulation Peptides Proteins Quantum Theory Solutions Tyrosine Water
description	Experimental studies in hemeproteins and model Tyr/Cys-containing peptides exposed to oxidizing and nitrating species suggest that intramolecular electron transfer (IET) between tyrosyl radicals (Tyr-O) and Cys residues controls oxidative modification yields. The molecular basis of this IET process is not sufficiently understood with structural atomic detail. Herein, we analyzed using molecular dynamics and quantum mechanics-based computational calculations, mechanistic possibilities for the radical transfer reaction in Tyr/Cys-containing peptides in solution and correlated them with existing experimental data. Our results support that Tyr-O to Cys radical transfer is mediated by an acid/base equilibrium that involves deprotonation of Cys to form the thiolate, followed by a likely rate-limiting transfer process to yield cysteinyl radical and a Tyr phenolate; proton uptake by Tyr completes the reaction. Both, the pKa values of the Tyr phenol and Cys thiol groups and the energetic and kinetics of the reversible IET are revealed as key physico-chemical factors. The proposed mechanism constitutes a case of sequential, acid/base equilibrium-dependent and solvent-mediated, proton-coupled electron transfer and explains the dependency of oxidative yields in Tyr/Cys peptides as a function of the number of alanine spacers. These findings contribute to explain oxidative modifications in proteins that contain sequence and/or spatially close Tyr-Cys residues. © 2012 Elsevier Inc. All rights reserved.
author	Petruk, Ariel Alcides Estrin, Dario Ariel Murgida, Daniel Horacio Martí, Marcelo Adrián
author_facet	Petruk, Ariel Alcides Estrin, Dario Ariel Murgida, Daniel Horacio Martí, Marcelo Adrián
author_sort	Petruk, Ariel Alcides
title	Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution
title_short	Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution
title_full	Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution
title_fullStr	Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution
title_full_unstemmed	Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution
title_sort	molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: computer simulation studies in model tyrosine-cysteine peptides in solution
publishDate	2012
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00039861_v525_n1_p82_Petruk http://hdl.handle.net/20.500.12110/paper_00039861_v525_n1_p82_Petruk
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_version_	1768544251470151680

Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution

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