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Dual role of the active-center cysteine in human peroxiredoxin 1 : Peroxidase activity and heme binding


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タイトル: Dual role of the active-center cysteine in human peroxiredoxin 1 : Peroxidase activity and heme binding
著者: Watanabe, Yuta 著作を一覧する
Ishimori, Koichiro 著作を一覧する
Uchida, Takeshi 著作を一覧する
キーワード: Heme
Cytosolic heme-binding protein
発行日: 2017年 2月12日
出版者: Elsevier
誌名: Biochemical and biophysical research communications
巻: 483
号: 3
開始ページ: 930
終了ページ: 935
出版社 DOI: 10.1016/j.bbrc.2017.01.034
抄録: HBP23, a 23-kDa heme-binding protein identified in rats, is a member of the peroxiredoxin (Prx) family, the primary peroxidases involved in hydrogen peroxide catabolism. Although HBP23 has a characteristic Cys-Pro heme-binding motif, the significance of heme binding to Prx family proteins remains to be elucidated. Here, we examined the effect of heme binding to human peroxiredoxin-1 (PRX1), which has 97% amino acid identity to HBP23. PRX1 was expressed in Escherichia coli and purified to homogeneity. Spectroscopic titration demonstrated that PRX1 binds heme with a 1:1 stoichiometry and a dissociation constant of 0.17 mu M. UV-vis spectra of heme-PRX1 suggested that Cys52 is the axial ligand of ferric heme. PRX1 peroxidase activity was lost upon heme binding, reflecting the fact that Cys52 is not only the heme-binding site but also the active center of peroxidase activity. Interestingly, heme binding to PRX1 caused a decrease in the toxicity and degradation of heme, significantly suppressing H2O2-dependent heme peroxidase activity and degradation of PRX1-bound heme compared with that of free hemin. By virtue of its cytosolic abundance (similar to 20 mu M), PRX1 thus functions as a scavenger of cytosolic hemin (<1 mu M). Collectively, our results indicate that PRX1 has a dual role; Cys-dependent peroxidase activity and cytosolic heme scavenger. (C) 2017 Elsevier Inc. All rights reserved.
Rights: © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
資料タイプ: article (author version)
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 内田 毅


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