3C0Y

Crystal structure of catalytic domain of human histone deacetylase HDAC7

「2NVR」から置き換えられました 「2I4Y」から置き換えられました

3C0Y の概要

• エントリーDOI: 10.2210/pdb3c0y/pdb
• 関連するPDBエントリー: 2NVR 3C0Z 3C10
• 分子名称: Histone deacetylase 7a, ZINC ION, POTASSIUM ION, ... (4 entities in total)
• 機能のキーワード: histone deacetylase, structural genomics, structural genomics consortium, sgc, alternative splicing, chromatin regulator, cytoplasm, hydrolase, nucleus, phosphoprotein, polymorphism, repressor, transcription, transcription regulation
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q8WUI4
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 137182.06

構造登録者

Min, J.R.,Schuetz, A.,Allali-Hassani, A.,Loppnau, P.,Kwiatkowski, N.P.,Mazitschek, R.,Weigelt, J.,Sundstrom, M.,Arrowsmith, C.H.,Edwards, A.M.,Vedadi, M.,Bochkarev, A.,Plotnikov, A.N.,Structural Genomics Consortium (SGC) (登録日: 2008-01-21, 公開日: 2008-02-19, 最終更新日: 2023-08-30)

主引用文献

Schuetz, A.,Min, J.,Allali-Hassani, A.,Schapira, M.,Shuen, M.,Loppnau, P.,Mazitschek, R.,Kwiatkowski, N.P.,Lewis, T.A.,Maglathin, R.L.,McLean, T.H.,Bochkarev, A.,Plotnikov, A.N.,Vedadi, M.,Arrowsmith, C.H.
Human HDAC7 harbors a class IIa histone deacetylase-specific zinc binding motif and cryptic deacetylase activity.
J.Biol.Chem., 283:11355-11363, 2008

PubMed Abstract: Histone deacetylases (HDACs) are protein deacetylases that play a role in repression of gene transcription and are emerging targets in cancer therapy. Here, we characterize the structure and enzymatic activity of the catalytic domain of human HDAC7 (cdHDAC7). Although HDAC7 normally exists as part of a multiprotein complex, we show that cdHDAC7 has a low level of deacetylase activity which can be inhibited by known HDAC inhibitors. The crystal structures of human cdHDAC7 and its complexes with two hydroxamate inhibitors are the first structures of the catalytic domain of class IIa HDACs and demonstrate significant differences with previously reported class I and class IIb-like HDAC structures. We show that cdHDAC7 has an additional class IIa HDAC-specific zinc binding motif adjacent to the active site which is likely to participate in substrate recognition and protein-protein interaction and may provide a site for modulation of activity. Furthermore, a different active site topology results in modified catalytic properties and in an enlarged active site pocket. Our studies provide mechanistic insights into class IIa HDACs and facilitate the design of specific modulators.

PubMed: 18285338
DOI: 10.1074/jbc.M707362200

実験手法

X-RAY DIFFRACTION (2.1 Å)