1T69

Crystal Structure of human HDAC8 complexed with SAHA

1T69 の概要

• エントリーDOI: 10.2210/pdb1t69/pdb
• 関連するPDBエントリー: 1T64 1T67
• 分子名称: Histone deacetylase 8, ZINC ION, OCTANEDIOIC ACID HYDROXYAMIDE PHENYLAMIDE (3 entities in total)
• 機能のキーワード: histone deacetylase, zinc hydrolase, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q9BY41
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42132.21

構造登録者

Somoza, J.R.,Skene, R.J.,Katz, B.A.,Mol, C.,Ho, J.D.,Jennings, A.J.,Luong, C.,Arvai, A.,Buggy, J.J.,Chi, E.,Tang, J.,Sang, B.-C.,Verner, E.,Wynands, R.,Leahy, E.M.,Dougan, D.R.,Snell, G.,Navre, M.,Knuth, M.W.,Swanson, R.V.,McRee, D.E.,Tari, L.W. (登録日: 2004-05-05, 公開日: 2004-07-27, 最終更新日: 2023-08-23)

主引用文献

Somoza, J.R.,Skene, R.J.,Katz, B.A.,Mol, C.,Ho, J.D.,Jennings, A.J.,Luong, C.,Arvai, A.,Buggy, J.J.,Chi, E.,Tang, J.,Sang, B.-C.,Verner, E.,Wynands, R.,Leahy, E.M.,Dougan, D.R.,Snell, G.,Navre, M.,Knuth, M.W.,Swanson, R.V.,McRee, D.E.,Tari, L.W.
Structural Snapshots of Human HDAC8 Provide Insights into the Class I Histone Deacetylases
Structure, 12:1325-1334, 2004

PubMed Abstract: Modulation of the acetylation state of histones plays a pivotal role in the regulation of gene expression. Histone deacetylases (HDACs) catalyze the removal of acetyl groups from lysines near the N termini of histones. This reaction promotes the condensation of chromatin, leading to repression of transcription. HDAC deregulation has been linked to several types of cancer, suggesting a potential use for HDAC inhibitors in oncology. Here we describe the first crystal structures of a human HDAC: the structures of human HDAC8 complexed with four structurally diverse hydroxamate inhibitors. This work sheds light on the catalytic mechanism of the HDACs, and on differences in substrate specificity across the HDAC family. The structure also suggests how phosphorylation of Ser39 affects HDAC8 activity.

PubMed: 15242608
DOI: 10.1016/j.str.2004.04.012

実験手法

X-RAY DIFFRACTION (2.91 Å)