3K3O

Crystal structure of the catalytic core domain of human PHF8 complexed with alpha-ketoglutarate

3K3O の概要

• エントリーDOI: 10.2210/pdb3k3o/pdb
• 関連するPDBエントリー: 3K3N
• 分子名称: PHD finger protein 8, 2-OXOGLUTARIC ACID, FE (II) ION, ... (4 entities in total)
• 機能のキーワード: phf8 (phd finger protein 8), histone demethylase, chromatin modification, methylated h3k9, mental retardation, metal-binding, phosphoprotein, zinc-finger, oxidoreductase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43481.29

構造登録者

Yu, L.,Wang, Y.,Huang, S.,Wang, J.,Deng, Z.,Wu, W.,Gong, W.,Chen, Z. (登録日: 2009-10-03, 公開日: 2010-01-19, 最終更新日: 2023-11-01)

主引用文献

Yu, L.,Wang, Y.,Huang, S.,Wang, J.,Deng, Z.,Zhang, Q.,Wu, W.,Zhang, X.,Liu, Z.,Gong, W.,Chen, Z.
Structural insights into a novel histone demethylase PHF8
Cell Res., 20:166-173, 2010

PubMed Abstract: Dynamic regulation of histone methylation/demethylation plays an important role during development. Mutations and truncations in human plant homeodomain (PHD) finger protein 8 (PHF8) are associated with X-linked mental retardation and facial anomalies, such as a long face, broad nasal tip, cleft lip/cleft palate and large hands, yet its molecular function and structural basis remain unclear. Here, we report the crystal structures of the catalytic core of PHF8 with or without alpha-ketoglutarate (alpha-KG) at high resolution. Biochemical and structural studies reveal that PHF8 is a novel histone demethylase specific for di- and mono-methylated histone H3 lysine 9 (H3K9me2/1), but not for H3K9me3. Our analyses also reveal how human PHF8 discriminates between methylation states and achieves sequence specificity for methylated H3K9. The in vitro demethylation assay also showed that the F279S mutant observed in clinical patients possesses no demethylation activity, suggesting that loss of enzymatic activity is crucial for pathogenesis of PHF8 patients. Taken together, these results will shed light on the molecular mechanism underlying PHF8-associated developmental and neurological diseases.

PubMed: 20101266
DOI: 10.1038/cr.2010.8

実験手法

X-RAY DIFFRACTION (2.1 Å)