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ツゲ ヒデアキ
TSUGE HIDEAKI
津下 英明 所属 京都産業大学 生命科学部 先端生命科学科 職種 教授 |
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| 言語種別 | 英語 |
| 発行・発表の年月 | 2011/12 |
| 形態種別 | 研究論文 |
| 査読 | 査読あり |
| 標題 | Structural Basis of Free Reduced Flavin Generation by Flavin Reductase from Thermus thermophilus HB8 |
| 執筆形態 | その他 |
| 掲載誌名 | JOURNAL OF BIOLOGICAL CHEMISTRY |
| 出版社・発行元 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| 巻・号・頁 | 286(51),pp.44078-44085 |
| 担当区分 | 最終著者,責任著者 |
| 著者・共著者 | Takahito Imagawa,Toshiharu Tsurumura,Yasushi Sugimoto,Kenji Aki,Kazumi Ishidoh,Seiki Kuramitsu,Hideaki Tsuge |
| 概要 | Free reduced flavins are involved in a variety of biological functions. They are generated from NAD(P)H by flavin reductase via co-factor flavin bound to the enzyme. Although recent findings on the structure and function of flavin reductase provide new information about co-factor FAD and substrate NAD, there have been no reports on the substrate flavin binding site. Here we report the structure of TTHA0420 from Thermus thermophilus HB8, which belongs to flavin reductase, and describe the dual binding mode of the substrate and co-factor flavins. We also report that TTHA0420 has not only the flavin reductase motif GDH but also a specific motif YGG in C terminus as well as Phe-41 and Arg-11, which are conserved in its subclass. From the structure, these motifs are important for the substrate flavin binding. On the contrary, the C terminus is stacked on the NADH binding site, apparently to block NADH binding to the active site. To identify the function of the C-terminal region, we designed and expressed a mutant TTHA0420 enzyme in which the C-terminal five residues were deleted (TTHA0420-Delta C5). Notably, the activity of TTHA0420-Delta C5 was about 10 times higher than that of the wild-type enzyme at 20-40 degrees C. Our findings suggest that the C-terminal region of TTHA0420 may regulate the alternative binding of NADH and substrate flavin to the enzyme. |
| DOI | 10.1074/jbc.M111.257824 |
| ISSN | 0021-9258 |