1ZZ3

Crystal structure of a HDAC-like protein with CypX bound

1ZZ3 の概要

• エントリーDOI: 10.2210/pdb1zz3/pdb
• 関連するPDBエントリー: 1ZZ0 1ZZ1
• 分子名称: Histone deacetylase-like amidohydrolase, 3-CYCLOPENTYL-N-HYDROXYPROPANAMIDE, ZINC ION, ... (5 entities in total)
• 機能のキーワード: hydrolase
• 由来する生物種: Alcaligenaceae bacterium
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 158901.67

構造登録者

Nielsen, T.K.,Hildmann, C.,Dickmanns, A.,Schwienhorst, A.,Ficner, R. (登録日: 2005-06-13, 公開日: 2005-11-29, 最終更新日: 2024-03-13)

主引用文献

Nielsen, T.K.,Hildmann, C.,Dickmanns, A.,Schwienhorst, A.,Ficner, R.
Crystal structure of a bacterial class 2 histone deacetylase homologue
J.Mol.Biol., 354:107-120, 2005

PubMed Abstract: Histone deacetylases (HDACs) are among the most promising targets in cancer therapy. However, structural information greatly enhancing the design of HDAC inhibitors as novel chemotherapeutics has not been available on class 2 HDACs so far. Here we present the structure of the bacterial FB188 HDAH (histone deacetylase-like amidohydrolase from Bordetella/Alcaligenes strain FB188) that reveals high sequential and functional homology to human class 2 HDACs. FB188 HDAH is capable to remove the acetyl moiety from acetylated histones. Several HDAC-specific inhibitors, which have been shown to inhibit tumor activity in both pre-clinical models and in clinical trials, also inhibit FB188 HDAH. We have determined the crystal structure of FB188 HDAH at a resolution of 1.6 angstroms in complex with the reaction product acetate, as well as in complex with the inhibitors suberoylanilide hydroxamic acid (SAHA) and cyclopentyle-propionyle hydroxamic acid (CypX) at a resolution of 1.57 angstroms and 1.75 angstroms, respectively. FB188 HDAH exhibits the canonical fold of class 1 HDACs and contains a catalytic zinc ion. The highest structural diversity compared to class 1 enzymes is found in loop regions especially in the area around the entrance of the active site, indicating significant differences among the acetylated proteins binding to class 1 and 2 HDACs, respectively.

PubMed: 16242151
DOI: 10.1016/j.jmb.2005.09.065

実験手法

X-RAY DIFFRACTION (1.76 Å)