Transition state and encounter complex for fast association of cytochrome c2 with bacterial reaction center

Electrostatic interactions strongly enhance the electron transfer reaction between cytochrome (Cyt) c(2) and reaction center (RC) from photosynthetic bacteria, yielding a second-order rate constant, k(2) approximately 10(9) s(-1).M(-1), close to the diffusion limit. The proposed mechanism involves an encounter complex (EC) stabilized by electrostatic interactions, followed by a transition state (TS), leading to the bound complex active in electron transfer. The effect of electrostatic interactions was previously studied by Tetreault et al. [Tetreault, M., Cusanovich, M., Meyer, T., Axelrod, H. & Okamura, M. Y. (2002) Biochemistry 41, 5807-5815] by measuring k(2) for RC and Cyt molecules with modified charged residues at the binding interface. The present work is a computational analysis of this kinetic study to determine the ensemble of configurations of the TS and EC. Changes in the TS energies due to different mutations were compared with differences in the calculated electrostatic energies for a wide range of Cyt/RC configurations. The TS ensemble, obtained from structures having the highest correlation coefficients in the comparison with experimental data, has the Cyt displaced by approximately 10 A from its position in x-ray crystal structure, close to the average position of the EC ensemble, with strong electrostatic interactions between Cyt on the M subunit side of the RC surface. The heme of the Cyt is oriented toward Tyr L162 on the RC, the tunneling contact in the bound final state on the RC. The similarity between the structures of the EC, TS, and bound state can account for the rapid rate of association responsible for fast diffusion-controlled electron transfer.