Molecular basis for the electric field modulation of cytochrome c structure and function

Cytochrome c (Cyt) is a small soluble heme protein with a hexacoordinated heme and functions as an electron shuttle in the mitochondria and in early events of apoptosis when released to the cytoplasm. Using molecular dynamics simulations, we show here that biologically relevant electric fields induc...

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Autores principales:	De Biase, P.M., Paggi, D.A., Doctorovich, F., Hildebrandt, P., Estrin, D.A., Murgida, D.H., Marti, M.A.
Formato:	JOUR
Materias:	Apoptosis Axial ligand Conformational change Conformational transitions Cytochrome C Electric field modulation Electron shuttle Electron-transfer reactions Heme iron Heme proteins High spins Molecular basis Molecular dynamics simulations Pentacoordinated Peroxidase activities Protein segments Reduction potential Respiratory chains Structural distortions Structural effect Cell death Electric fields Mitochondria Molecular dynamics Porphyrins Reaction kinetics Redox reactions Hemoglobin cytochrome c heme hemoprotein iron peroxidase article conformational transition electric field electron transport enzyme structure molecular dynamics oxidation reduction reaction protein function simulation Cytochromes c Heme Ligands Molecular Dynamics Simulation Oxidation-Reduction Peroxidases Protein Conformation Static Electricity Thermodynamics
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00027863_v131_n44_p16248_DeBiase
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_00027863_v131_n44_p16248_DeBiase
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spelling	todo:paper_00027863_v131_n44_p16248_DeBiase2023-10-03T13:54:11Z Molecular basis for the electric field modulation of cytochrome c structure and function De Biase, P.M. Paggi, D.A. Doctorovich, F. Hildebrandt, P. Estrin, D.A. Murgida, D.H. Marti, M.A. Apoptosis Axial ligand Conformational change Conformational transitions Cytochrome C Electric field modulation Electron shuttle Electron-transfer reactions Heme iron Heme proteins High spins Molecular basis Molecular dynamics simulations Pentacoordinated Peroxidase activities Protein segments Reduction potential Respiratory chains Structural distortions Structural effect Cell death Electric fields Mitochondria Molecular dynamics Porphyrins Reaction kinetics Redox reactions Hemoglobin cytochrome c heme hemoprotein iron peroxidase article conformational transition electric field electron transport enzyme structure molecular dynamics oxidation reduction reaction protein function simulation Apoptosis Cytochromes c Heme Ligands Molecular Dynamics Simulation Oxidation-Reduction Peroxidases Protein Conformation Static Electricity Thermodynamics Cytochrome c (Cyt) is a small soluble heme protein with a hexacoordinated heme and functions as an electron shuttle in the mitochondria and in early events of apoptosis when released to the cytoplasm. Using molecular dynamics simulations, we show here that biologically relevant electric fields induce an increased mobility and structural distortion of key protein segments that leads to the detachment of the sixth axial ligand Met80 from the heme iron. This electric-field-induced conformational transition is energetically and entropically driven and leads to a pentacoordinated high spin heme that is characterized by a drastically lowered reduction potential as well as by an increased peroxidase activity. The simulations provide a detailed atomistic picture of the structural effects of the electric field on the structure of Cyt, which allows a sound interpretation of recent experimental results. The observed conformational change may modulate the electron transfer reactions of Cyt in the mitochondria and, furthermore, may constitute a switch from the redox function in the respiratory chain to the peroxidase function in the early events of apoptosis. © 2009 American Chemical Society. Fil:De Biase, P.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Doctorovich, F. 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.H. 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00027863_v131_n44_p16248_DeBiase
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Apoptosis Axial ligand Conformational change Conformational transitions Cytochrome C Electric field modulation Electron shuttle Electron-transfer reactions Heme iron Heme proteins High spins Molecular basis Molecular dynamics simulations Pentacoordinated Peroxidase activities Protein segments Reduction potential Respiratory chains Structural distortions Structural effect Cell death Electric fields Mitochondria Molecular dynamics Porphyrins Reaction kinetics Redox reactions Hemoglobin cytochrome c heme hemoprotein iron peroxidase article conformational transition electric field electron transport enzyme structure molecular dynamics oxidation reduction reaction protein function simulation Apoptosis Cytochromes c Heme Ligands Molecular Dynamics Simulation Oxidation-Reduction Peroxidases Protein Conformation Static Electricity Thermodynamics
spellingShingle	Apoptosis Axial ligand Conformational change Conformational transitions Cytochrome C Electric field modulation Electron shuttle Electron-transfer reactions Heme iron Heme proteins High spins Molecular basis Molecular dynamics simulations Pentacoordinated Peroxidase activities Protein segments Reduction potential Respiratory chains Structural distortions Structural effect Cell death Electric fields Mitochondria Molecular dynamics Porphyrins Reaction kinetics Redox reactions Hemoglobin cytochrome c heme hemoprotein iron peroxidase article conformational transition electric field electron transport enzyme structure molecular dynamics oxidation reduction reaction protein function simulation Apoptosis Cytochromes c Heme Ligands Molecular Dynamics Simulation Oxidation-Reduction Peroxidases Protein Conformation Static Electricity Thermodynamics De Biase, P.M. Paggi, D.A. Doctorovich, F. Hildebrandt, P. Estrin, D.A. Murgida, D.H. Marti, M.A. Molecular basis for the electric field modulation of cytochrome c structure and function
topic_facet	Apoptosis Axial ligand Conformational change Conformational transitions Cytochrome C Electric field modulation Electron shuttle Electron-transfer reactions Heme iron Heme proteins High spins Molecular basis Molecular dynamics simulations Pentacoordinated Peroxidase activities Protein segments Reduction potential Respiratory chains Structural distortions Structural effect Cell death Electric fields Mitochondria Molecular dynamics Porphyrins Reaction kinetics Redox reactions Hemoglobin cytochrome c heme hemoprotein iron peroxidase article conformational transition electric field electron transport enzyme structure molecular dynamics oxidation reduction reaction protein function simulation Apoptosis Cytochromes c Heme Ligands Molecular Dynamics Simulation Oxidation-Reduction Peroxidases Protein Conformation Static Electricity Thermodynamics
description	Cytochrome c (Cyt) is a small soluble heme protein with a hexacoordinated heme and functions as an electron shuttle in the mitochondria and in early events of apoptosis when released to the cytoplasm. Using molecular dynamics simulations, we show here that biologically relevant electric fields induce an increased mobility and structural distortion of key protein segments that leads to the detachment of the sixth axial ligand Met80 from the heme iron. This electric-field-induced conformational transition is energetically and entropically driven and leads to a pentacoordinated high spin heme that is characterized by a drastically lowered reduction potential as well as by an increased peroxidase activity. The simulations provide a detailed atomistic picture of the structural effects of the electric field on the structure of Cyt, which allows a sound interpretation of recent experimental results. The observed conformational change may modulate the electron transfer reactions of Cyt in the mitochondria and, furthermore, may constitute a switch from the redox function in the respiratory chain to the peroxidase function in the early events of apoptosis. © 2009 American Chemical Society.
format	JOUR
author	De Biase, P.M. Paggi, D.A. Doctorovich, F. Hildebrandt, P. Estrin, D.A. Murgida, D.H. Marti, M.A.
author_facet	De Biase, P.M. Paggi, D.A. Doctorovich, F. Hildebrandt, P. Estrin, D.A. Murgida, D.H. Marti, M.A.
author_sort	De Biase, P.M.
title	Molecular basis for the electric field modulation of cytochrome c structure and function
title_short	Molecular basis for the electric field modulation of cytochrome c structure and function
title_full	Molecular basis for the electric field modulation of cytochrome c structure and function
title_fullStr	Molecular basis for the electric field modulation of cytochrome c structure and function
title_full_unstemmed	Molecular basis for the electric field modulation of cytochrome c structure and function
title_sort	molecular basis for the electric field modulation of cytochrome c structure and function
url	http://hdl.handle.net/20.500.12110/paper_00027863_v131_n44_p16248_DeBiase
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_version_	1807315851789991936

Molecular basis for the electric field modulation of cytochrome c structure and function

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