書誌事項
- タイトル別名
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- Structural Basis for Ca2+-induced Activation for Human PAD4
- サイキン ノ ケンキュウ カラ カルシウム ケツゴウ ニ ヨッテ カッセイカ サレル ヒストン シュウショク コウソ PAD4 ノ コウゾウ カガクテキ キバン
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説明
Peptidylarginine deimianse 4 (PAD4) is a Ca2+-dependent enzyme that catalyzes the conversion of both arginine and mono-methyl arginine in histones into citrullines, and regulates both histone argininine methylation level and gene activity. Its gene is susceptibility locus for rheumatoid arthritis (RA) . Here we present the crystal structure of Ca2+-free wild-type PAD4, which shows that the polypeptide chain adopts an elongated fold in which the N-terminal domain forms two immunoglobulin-like subdomains, and the C-terminal domain forms an α/β propeller structure. Five Ca2+-binding sites, none of which adopts an EF-hand motif, were identified in the structure of a Ca2+-bound inactive mutant with and without bound substrate. These structural data indicate that Ca2+binding induces conformational changes that generate the active site cleft. Our findings identify a novel mechanism for enzyme activation by Ca2+ions, and are important for understanding the mechanism of protein citrullination and for developing PAD-inhibiting drugs for the treatment of RA.
収録刊行物
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- 日本結晶学会誌
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日本結晶学会誌 47 (4), 268-273, 2005
日本結晶学会
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詳細情報 詳細情報について
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- CRID
- 1390001204086769536
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- NII論文ID
- 130000800473
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- NII書誌ID
- AN00188364
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- ISSN
- 18845576
- 03694585
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- NDL書誌ID
- 7473657
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可