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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paper:paper_00027863_v131_n44_p16248_DeBiase2023-06-08T14:22:46Z Molecular basis for the electric field modulation of cytochrome c structure and function De Biase, Pablo Martín Doctorovich, Fabio Ariel Estrin, Dario Ariel Murgida, Daniel Horacio Martí, Marcelo Adrián 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. 2009 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00027863_v131_n44_p16248_DeBiase 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, Pablo Martín Doctorovich, Fabio Ariel Estrin, Dario Ariel Murgida, Daniel Horacio Martí, Marcelo Adrián 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. |
| author |
De Biase, Pablo Martín Doctorovich, Fabio Ariel Estrin, Dario Ariel Murgida, Daniel Horacio Martí, Marcelo Adrián |
| author_facet |
De Biase, Pablo Martín Doctorovich, Fabio Ariel Estrin, Dario Ariel Murgida, Daniel Horacio Martí, Marcelo Adrián |
| author_sort |
De Biase, Pablo Martín |
| 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 |
| publishDate |
2009 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00027863_v131_n44_p16248_DeBiase http://hdl.handle.net/20.500.12110/paper_00027863_v131_n44_p16248_DeBiase |
| work_keys_str_mv |
AT debiasepablomartin molecularbasisfortheelectricfieldmodulationofcytochromecstructureandfunction AT doctorovichfabioariel molecularbasisfortheelectricfieldmodulationofcytochromecstructureandfunction AT estrindarioariel molecularbasisfortheelectricfieldmodulationofcytochromecstructureandfunction AT murgidadanielhoracio molecularbasisfortheelectricfieldmodulationofcytochromecstructureandfunction AT martimarceloadrian molecularbasisfortheelectricfieldmodulationofcytochromecstructureandfunction |
| _version_ |
1768541728138067968 |