Polarizability of the Active Site in Enzymatic Catalysis: Cytochrome c

Anisotropic polarizability of the heme in cytochrome c is foun to be a major factor in suppressing the activation barrier of protein electron transfer (catalytic effect). Polarizability couples to the electric fiel of protein an water to enhance fluctuations of the electron-transfer energy gap an the corresponing variance reorganization energy^var. The reorganization energy observable by kinetic measurements^r = (λ^St)²/λ^var is compose of^var an the Stokes-shift reorganization energy^St. It is lowere compare to the usually reporte^St ue to polarizability of the active site leaing to^var >^St. The coupling of electrostatic protein-water fluctuations to the polarizable active site is accounte for here by empirical valence-bon iagonalization of the active-site Hamiltonian along the simulation trajectory. We show that recent simulations employing this technique, which faile to fin the effect of polarizability on electron-transfer kinetics, were erroneous in neglecting the iagonal ipole moments in the Hamiltonian matrix an failing to rotate the electric fiel prouce by the protein-water meium into the molecular frame of the active site. We fin that anisotropy of the tensor of polarizability ifference in the two oxiation states of the heme matches anisotropy of the secon-rank tensor constructe from the electric fiel at the active site. Exposure of the heme to water from only one sie carries significant catalytic function, irectly leaing to the fiel anisotropy an the corresponing epression of the activation barrier.