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Originally published In Press as doi:10.1074/jbc.M008501200 on October 25, 2000
J. Biol. Chem., Vol. 276, Issue 4, 2786-2789, January 26, 2001
Adrenodoxin Reductase-Adrenodoxin Complex Structure Suggests
Electron Transfer Path in Steroid Biosynthesis*
Jürgen J.
Müller §,
Anna
Lapko ¶,
Gleb
Bourenkov ,
Klaus
Ruckpaul , and
Udo
Heinemann **
From Max-Delbrück-Centrum für Molekulare
Medizin, Robert-Rössle-Strasse 10, D-13125 Berlin,
MPG-ASMB, c/o DESY, Notkestrasse 85, D-22603 Hamburg, and
** Institut für Chemie-Kristallographie, Freie
Universität Berlin, Takustrasse 6, D-14195 Berlin, Germany
The steroid hydroxylating system of adrenal
cortex mitochondria consists of the membrane-attached
NADPH-dependent adrenodoxin reductase (AR), the soluble
one-electron transport protein adrenodoxin (Adx), and a
membrane-integrated cytochrome P450 of the CYP11 family. In the 2.3-Å
resolution crystal structure of the Adx·AR complex, 580 Å2 of partly polar surface are buried. Main
interaction sites are centered around Asp79,
Asp76, Asp72, and Asp39 of Adx and
around Arg211, Arg240, Arg244, and
Lys27 of AR, respectively. In particular, the region around
Asp39 defines a new protein interaction site for Adx,
similar to those found in plant and bacterial ferredoxins. Additional
contacts involve the electron transfer region between the redox centers of AR and Adx and C-terminal residues of Adx. The Adx residues Asp113 to Arg115 adopt 310-helical
conformation and engage in loose intermolecular contacts within a deep
cleft of AR. Complex formation is accompanied by a slight domain
rearrangement in AR. The [2Fe-2S] cluster of Adx and the
isoalloxazine rings of FAD of AR are 10 Å apart suggesting a possible
electron transfer route between these redox centers. The AR·Adx
complex represents the first structure of a biologically relevant
complex between a ferredoxin and its reductase.
*
This work was supported by Deutsche Forschungsgemeinschaft
Grants He 1318/19-1 and WER436 and the Fonds der Chemischen Industrie.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
The atomic coordinates and the structure factors (code 1e6e) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).
§
To whom correspondence may be addressed. Tel.: 49 30 9406 3421;
E-mail: JJM@MDC-Berlin.de.
¶
On leave from the International Sakharow Institute of
Radioecology, 2220009 Minsk, Belarus.

To whom correspondence may be addressed. Tel.: 49 30 9406-3420;
E-mail: Heinemann@MDC-Berlin.de.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
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