Molecular Basis for the Electric Field Modulation of Cytochrome c Structure and Function

DE BIASE, P.; ALVAREZ PAGGI, D.; DOCTOROVICH, F.; HILDEBRANDT, P.; ESTRIN, D.A.; MURGIDA, D.H.; MARTI, M.A.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

AMER CHEMICAL SOC

Lugar: Columbus; Año: 2009 vol. 131 p. 16248 - 16256

0002-7863

Abstract: Cytochrome c (Cyt) is a small soluble heme protein with a hexacoordinated heme and functionsas 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 anincreased mobility and structural distortion of key protein segments that leads to the detachment of thesixth axial ligand Met80 from the heme iron. This electric-field-induced conformational transition isenergetically and entropically driven and leads to a pentacoordinated high spin heme that is characterizedby a drastically lowered reduction potential as well as by an increased peroxidase activity. The simulationsprovide 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 changemay modulate the electron transfer reactions of Cyt in the mitochondria and, furthermore, may constitutea switch from the redox function in the respiratory chain to the peroxidase function in the early events ofapoptosis.