6THV

X-ray structure of the Danio rerio histone deacetylase 6 (HDAC6; catalytic domain 2) in complex with Tubastatin A

6THV の概要

• エントリーDOI: 10.2210/pdb6thv/pdb
• 分子名称: Histone deacetylase 6, ZINC ION, POTASSIUM ION, ... (10 entities in total)
• 機能のキーワード: histone deacetylase 6, tubastatin a, hydrolase
• 由来する生物種: Danio rerio (Zebrafish)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40984.85

構造登録者

Barinka, C.,Motlova, L.,Svoboda, M. (登録日: 2019-11-21, 公開日: 2020-07-15, 最終更新日: 2024-01-24)

主引用文献

Shen, S.,Svoboda, M.,Zhang, G.,Cavasin, M.A.,Motlova, L.,McKinsey, T.A.,Eubanks, J.H.,Barinka, C.,Kozikowski, A.P.
Structural and in Vivo Characterization of Tubastatin A, a Widely Used Histone Deacetylase 6 Inhibitor.
Acs Med.Chem.Lett., 11:706-712, 2020

PubMed Abstract: Tubastatin A, a tetrahydro-γ-carboline-capped selective HDAC6 inhibitor (HDAC6i), was rationally designed 10 years ago, and has become the best investigated HDAC6i to date. It shows efficacy in various neurological disease animal models, as HDAC6 plays a crucial regulatory role in axonal transport deficits, protein aggregation, as well as oxidative stress. In this work, we provide new insights into this HDAC6i by investigating the molecular basis of its interactions with HDAC6 through X-ray crystallography, determining its functional capability to elevate the levels of acetylated α-tubulin in vitro and in vivo, correlating PK/PD profiles to determine effective doses in plasma and brain, and finally assessing its therapeutic potential toward psychiatric diseases through use of the SmartCube screening platform.

PubMed: 32435374
DOI: 10.1021/acsmedchemlett.9b00560

実験手法

X-RAY DIFFRACTION (1.1 Å)