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

J Mol Biol. 1999 Jun 18;289(4):981-90. doi: 10.1006/jmbi.1999.2807.

Abstract

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 A resolution, and the structure of the respective recombinant enzyme at 1.7 A 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 P 450. 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 electron 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenodoxin / metabolism
  • Animals
  • Binding Sites
  • Cattle
  • Cytochrome P-450 Enzyme System / metabolism*
  • Electron Transport
  • Ferredoxin-NADP Reductase / chemistry*
  • Ferredoxin-NADP Reductase / metabolism
  • Flavin-Adenine Dinucleotide / metabolism
  • Glycosylation
  • Mitochondria / metabolism*
  • Models, Molecular
  • NADP / metabolism
  • Protein Conformation
  • Protein Folding
  • Steroids / biosynthesis*
  • Thioredoxin-Disulfide Reductase / chemistry

Substances

  • Steroids
  • Adrenodoxin
  • Flavin-Adenine Dinucleotide
  • NADP
  • Cytochrome P-450 Enzyme System
  • Ferredoxin-NADP Reductase
  • Thioredoxin-Disulfide Reductase