Structural basis for the electron transfer from an open form of NADPH-cytochrome P450 oxidoreductase to heme oxygenase

Masakazu Sugishima; Hideaki Sato; Yuichiro HigashimotoJiro HaradaKei WadaKeiichi FukuyamaMasato Noguchi

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Structural basis for the electron transfer from an open form of NADPH-cytochrome P450 oxidoreductase to heme oxygenase

机译：Structural basis for the electron transfer from an open form of NADPH-cytochrome P450 oxidoreductase to heme oxygenase

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NADPH-cytochrome P450 oxidoreductase (CPR) supplies electrons to various heme proteins including heme oxygenase (HO), which is a key enzyme for heme degradation. Electrons from NADPH flow first to flavin adenine dinucleotide, then to flavin mononucleotide (FMN), and finally to heme in the redox partner. For electron transfer from CPR to its redox partner, the "closed-open transition" of CPR is indispensable. Here, we demonstrate that a hinge-shortened CPR variant, which favors an open conformation, makes a stable complex with heme–HO-1 and can support the HO reaction, although its efficiency is extremely limited. Furthermore, we determined the crystal structure of the CPR variant in complex with heme–HO-1 at 4.3-? resolution. The crystal structure of a complex of CPR and its redox partner was previously unidentified. The distance between heme and FMN in this complex (6 ?) implies direct electron transfer from FMN to heme.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2014年第7期|2524-2529|共6页
作者
Masakazu Sugishima; Hideaki Sato; Yuichiro HigashimotoJiro HaradaKei WadaKeiichi FukuyamaMasato Noguchi;
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作者单位

Department of Medical Biochemistry, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan;

Department of Chemistry, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan;

Organization for Promotion of Tenure Track, University of Miyazaki, Kiyotake, Miyazaki 889-1692, JapanDepartment of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871, Japan;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Structural; electron; oxygenase;

Structural basis for the electron transfer from an open form of NADPH-cytochrome P450 oxidoreductase to heme oxygenase

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