TY - JOUR
T1 - The structure of adrenodoxin reductase of mitochondrial P450 systems
T2 - Electron transfer for steroid biosynthesis
AU - Ziegler, Gabriele A.
AU - Vonrhein, Clemens
AU - Hanukoglu, Israel
AU - Schulz, Georg E.
N1 - Funding Information:
We thank the EMBL-team (Hamburg) for helping with synchrotron data collection. We further thank U. Heine-mann for providing the adrenodoxin coordinates prior to general release as well as T. Schwede and L. Maveyraud for discussions. This work was supported by the Deutsche Forschungsgemeinschaft under Sfb-388. G.A.Z. and C.V. contributed equally to this work.
PY - 1999/6/18
Y1 - 1999/6/18
N2 - 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.
AB - 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.
KW - Crystal structure
KW - Disulfide oxidoreductase
KW - Electron transferase
KW - Flavoenzyme
KW - MAD analysis
UR - http://www.scopus.com/inward/record.url?scp=0033057396&partnerID=8YFLogxK
U2 - 10.1006/jmbi.1999.2807
DO - 10.1006/jmbi.1999.2807
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C2 - 10369776
AN - SCOPUS:0033057396
SN - 0022-2836
VL - 289
SP - 981
EP - 990
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 4
ER -