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論文
- タイトル
- タイトル（英）
- The origin of esterase activity of Parkinson's disease causative factor DJ-1 implied by evolutionary trace analysis of its prokaryotic homolog HchA.
- 参照URL
- https://researchmap.jp/N-Matsuda/published_papers/46913857
- 著者
- 著者（英）
- Aiko Watanabe,Fumika Koyano,Kenichiro Imai,Yohei Hizukuri,Shizuka Ogiwara,Tomoya Ito,Jun Miyamoto,Chihiro Shibuya,Mayumi Kimura,Kazuya Toriumi,Chie Motono,Makoto Arai,Keiji Tanaka,Yoshinori Akiyama,Koji Yamano,Noriyuki Matsuda
- 担当区分
- 概要
- 概要（英）
- DJ-1, a causative gene for hereditary recessive Parkinsonism, is evolutionarily conserved across eukaryotes and prokaryotes. Structural analyses of DJ-1 and its homologs suggested the 106th Cys is a nucleophilic cysteine functioning as the catalytic center of hydratase or hydrolase activity. Indeed, DJ-1 and its homologs can convert highly electrophilic α-oxoaldehydes such as methylglyoxal into α-hydroxy acids as hydratase in vitro, and oxidation-dependent ester hydrolase (esterase) activity has also been reported for DJ-1. The mechanism underlying such plural activities, however, has not been fully characterized. To address this knowledge gap, we conducted a series of biochemical assays assessing the enzymatic activity of DJ-1 and its homologs. We found no evidence for esterase activity in any of the Escherichia coli DJ-1 homologs. Furthermore, contrary to previous reports, we found that oxidation inactivated rather than facilitated DJ-1 esterase activity. The E. coli DJ-1 homolog HchA possesses phenylglyoxalase and methylglyoxalase activities but lacks esterase activity. Since evolutionary trace analysis identified the 186th H as a candidate residue involved in functional differentiation between HchA and DJ-1, we focused on H186 of HchA and found that an esterase activity was acquired by H186A mutation. Introduction of reverse mutations into the equivalent position in DJ-1 (A107H) selectively eliminated its esterase activity without compromising α-oxoaldehyde hydratase activity. The obtained results suggest that differences in the amino acid sequences near the active site contributed to acquisition of esterase activity in vitro, and provide an important clue to the origin and significance of DJ-1 esterase activity.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- The Journal of biological chemistry
- 巻
- 号
- 開始ページ
- 107476
- 終了ページ
- 107476
- 出版年月
- 2024年6月13日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1016/j.jbc.2024.107476
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