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 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.
Ziegler
G A
GA
Albert-Ludwigs-Universität, Albertstrasse 21, Freiburg im Breisgau, D-79104, Germany.
Vonrhein
C
C
Hanukoglu
I
I
Schulz
G E
GE
D000325:Adrenodoxin / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004579:Electron Transport; D005287:Ferredoxin-NADP Reductase / Q000737:chemistry* / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D006031:Glycosylation; D008928:Mitochondria / Q000378:metabolism*; D008958:Models, Molecular; D009249:NADP / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D013256:Steroids / Q000096:biosynthesis*; D013880:Thioredoxin-Disulfide Reductase / Q000737:chemistry
D013256:Steroids; D000325:Adrenodoxin; D005182:Flavin-Adenine Dinucleotide; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D005287:Ferredoxin-NADP Reductase; D013880:Thioredoxin-Disulfide Reductase