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

Gabriele A. Ziegler, Clemens Vonrhein, Israel Hanukoglu, Georg E. Schulz

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)981-990
Number of pages10
JournalJournal of Molecular Biology
Volume289
Issue number4
DOIs
StatePublished - 18 Jun 1999

Keywords

  • Crystal structure
  • Disulfide oxidoreductase
  • Electron transferase
  • Flavoenzyme
  • MAD analysis

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