Electron transfer mediated by proteins is a key process in nature.
Many of the proteins involved in such electron transfers are complex and may require a number of redox active cofactors. In addition the electron-transfer steps themselves may add to the complexity by being coupled to other processes such as proton transfer and re-organisational changes. This is the case in the cytochromes P450 that function as steroidogenic enzymes. In fact, these enzymes exhibit three types of redox process: (i) electron-pair exchange (e.g. hydride transfer); (ii) transduction (i.e. where a system can accumulate reducing equivalents yet transfer them as single electrons); (iii) non-adiabatic electron transfer (i.e. the intra- or inter-molecular transfer of electrons between two weakly coupled redox centres). In the case of type-1 cytochromes P450 these redox processes are exemplified by three proteins: Ferredoxin reducatse, FdR; ferredoxin, Fd; and the cytochrome P450 itself. Hydride transfer (electron-pair exchange) occurs from NADPH to the FAD in FdR, followed by single electron transfers firstly from FdR to Fd and then from Fd to the heme of the P450, the site at which oxygen activation and steroidogenesis occur. The situation is somewhat different in the type-2 P450 s but the same general principles apply. The electron-transfer steps themselves can be modulated in a number of ways e.g. by the distance between redox-centres, by thermodynamics and by reorganisation energy etc. The availability of high-resolution crystal structures of many of these proteins, together with detailed biophysical and biochemical data, is allowing us to describe the rather subtle and elegant mechanisms by which these electron transfer steps are used to regulate/control enzyme function.
06 - 07 Nov 2006
Society for Endocrinology