INQUIMAE   12526
INSTITUTO DE QUIMICA, FISICA DE LOS MATERIALES, MEDIOAMBIENTE Y ENERGIA
Unidad Ejecutora - UE
artículos
Título:
Molecular basis of intramolecular electron transfer in proteins during radical-mediated oxidations: Computer simulation studies in model tyrosine-cysteine peptides in solution.
Autor/es:
ARIEL A PETRUK; SILVINA BARTESAGHI; MADIA TRUJILLO; DARIO A. ESTRIN; DANIEL H MURGIDA; B KALYANARAMAN; MARCELO A. MARTI; RAFAEL RADI
Revista:
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Editorial:
ELSEVIER SCIENCE INC
Referencias:
Lugar: Amsterdam; Año: 2012 p. 82 - 82
ISSN:
0003-9861
Resumen:
Experimental studies in hemeproteins and model Tyr/Cys-containing peptides exposed to oxidizing andnitrating species suggest that intramolecular electron transfer (IET) between tyrosyl radicals (Tyr-OÅ) andCys residues controls oxidative modification yields. The molecular basis of this IET process is not suffi-ciently understood with structural atomic detail. Herein, we analyzed using molecular dynamics andquantum mechanics-based computational calculations, mechanistic possibilities for the radical transferreaction in Tyr/Cys-containing peptides in solution and correlated them with existing experimental data.Our results support that Tyr-OÅ to Cys radical transfer is mediated by an acid/base equilibrium thatinvolves deprotonation of Cys to form the thiolate, followed by a likely rate-limiting transfer processto yield cysteinyl radical and a Tyr phenolate; proton uptake by Tyr completes the reaction. Both, thepKa values of the Tyr phenol and Cys thiol groups and the energetic and kinetics of the reversible IETare 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 explainsthe 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/orspatially close Tyr?Cys residues.