The structure of adrenodoxin reductase of mitochondrial P450 systems: Electron transfer for steroid biosynthesis

Adrenodoxin reductase is a monomeric 51 kDa flavoenzyme that is involved in the biosynthesis of all steroid hormones. The structure of the native bovine enzyme was determined at 2.8 Å resolution, and the structure of the respective recombinant enzyme at 1.7 Å resolution. Adrenodoxin reductase receives a two-electron package from NADPH and converts it to two single electrons that are transferred via adrenodoxin to all mitochondrial cytochromes P450. The structure suggests how the observed flavin semiquinone is stabilized. A striking feature is the asymmetric charge distribution which most likely controls the approach of the carrier adrenodoxin. A model for the interaction is proposed. Adrenodoxin reductase shows clear sequence homology to half a dozen proteins identified in genome analysis projects, but neither sequence nor structural homology to established, functionally related electron transferases. Yet, the structure revealed a relationship to the disulfide oxidoreductases, permitting the assignment of the NADP-binding site.