Crystal structure of a NADPH-cytochrome P450 oxidoreductase (CYPOR) and heme oxygenase 1 fusion protein implies a conformational change in CYPOR upon NADPH/NADP + binding

FEBS Letters

article

Masakazu Sugishima¹  Hideaki Sato¹  Kei Wada²  Ken Yamamoto¹ 

[1] Department of Medical Biochemistry, Kurume University School of Medicine;Department of Medical Sciences, University of Miyazaki

关键词: electron transfer;    protein–protein interaction;    conformation change;    X-ray crystallography;   

DOI  :  10.1002/1873-3468.13360

来源: John Wiley & Sons Ltd.

【 摘 要 】

Heme oxygenase-1 (HMOX1) catalyzes heme degradation utilizing reducing equivalents supplied from NADPH-cytochrome P450 reductase (CYPOR). Recently, we determined the complex structure of NADP+-bound openconformation stabilized CYPOR and heme-HMOX1, but the resolution was limited to 4.3 A. Here, we determined the crystal structure of the fusion protein of open-conformation stabilized CYPOR and heme-HMOX1 at 3.25 A resolution. Unexpectedly, no NADP+ was bound to this fusion protein in the crystal. Structural comparison of the NADP+-bound complex and the NADP+-free fusion protein suggests that NADP+ binding regulates the conformational change in the FAD-binding domain of CYPOR. As a result of this change, the FMN-binding domain of CYPOR approaches heme-bound HMOX1 upon NADP+ binding to enhance the electron-transfer efficiency from FMN to heme.

【 授权许可】

Unknown