3OPT

Crystal structure of the Rph1 catalytic core with a-ketoglutarate

3OPT の概要

• エントリーDOI: 10.2210/pdb3opt/pdb
• 関連するPDBエントリー: 3OPW
• 分子名称: DNA damage-responsive transcriptional repressor RPH1, 2-OXOGLUTARIC ACID, NICKEL (II) ION, ... (4 entities in total)
• 機能のキーワード: rph1, histone demethylase, catalytic core, oxidoreductase
• 由来する生物種: Saccharomyces cerevisiae (yeast)
• 細胞内の位置: Nucleus: P39956
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43818.40

構造登録者

Chang, Y.,Wu, J.,Tong, X.,Zhou, J.,Ding, J. (登録日: 2010-09-02, 公開日: 2010-12-22, 最終更新日: 2024-03-20)

主引用文献

Chang, Y.,Wu, J.,Tong, X.J.,Zhou, J.Q.,Ding, J.
Crystal structure of the catalytic core of Saccharomyces cerevesiae histone demethylase Rph1: insights into the substrate specificity and catalytic mechanism
Biochem.J., 433:295-302, 2011

PubMed Abstract: Saccharomyces cerevesiae Rph1 is a histone demethylase orthologous to human JMJD2A (Jumonji-domain-containing protein 2A) that can specifically demethylate tri- and di-methylated Lys³⁶ of histone H3. c-Rph1, the catalytic core of Rph1, is responsible for the demethylase activity, which is essential for the transcription elongation of some actively transcribed genes. In the present work, we report the crystal structures of c-Rph1 in apo form and in complex with Ni²(+) and α-KG [2-oxoglutarate (α-ketoglutarate)]. The structure of c-Rph1 is composed of a JmjN (Jumonji N) domain, a long β-hairpin, a mixed structural motif and a JmjC domain. The α-KG cofactor forms hydrogen-bonding interactions with the side chains of conserved residues, and the Ni²(+) ion at the active site is chelated by conserved residues and the cofactor. Structural comparison of Rph1 with JMJD2A indicates that the substrate-binding cleft of Rph1 is formed with several structural elements of the JmjC domain, the long β-hairpin and the mixed structural motif; and the methylated Lys³⁶ of H3 is recognized by several conserved residues of the JmjC domain. In vitro biochemical results show that mutations of the key residues at the catalytic centre and in the substrate-binding cleft abolish the demethylase activity. In vivo growth phenotype analyses also demonstrate that these residues are essential for its functional roles in transcription elongation. Taken together, our structural and biological data provide insights into the molecular basis of the histone demethylase activity and the substrate specificity of Rph1.

PubMed: 21067515
DOI: 10.1042/BJ20101418

実験手法

X-RAY DIFFRACTION (2.2 Å)