6ETS

Crystal structure of KDM4D with tetrazolhydrazide compound 1

6ETS の概要

• エントリーDOI: 10.2210/pdb6ets/pdb
• 分子名称: Lysine-specific demethylase 4D, ZINC ION, NICKEL (II) ION, ... (9 entities in total)
• 機能のキーワード: kdm4d, ligand binding, tetrazolhydrazide, tetrazole, inhibitor design, cancer, epigenetics, 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: 40507.07

構造登録者

Malecki, P.H.,Link, A.,Weiss, M.S.,Heinemann, U. (登録日: 2017-10-27, 公開日: 2019-02-20, 最終更新日: 2024-01-17)

主引用文献

Malecki, P.H.,Ruger, N.,Roatsch, M.,Krylova, O.,Link, A.,Jung, M.,Heinemann, U.,Weiss, M.S.
Structure-Based Screening of Tetrazolylhydrazide Inhibitors versus KDM4 Histone Demethylases.
Chemmedchem, 14:1828-1839, 2019

PubMed Abstract: Human histone demethylases are known to play an important role in the development of several tumor types. Consequently, they have emerged as important medical targets for the treatment of human cancer. Herein, structural studies on tetrazolylhydrazide inhibitors as a new scaffold for a certain class of histone demethylases, the JmjC proteins, are reported. A series of compounds are structurally described and their respective binding modes to the KDM4D protein, which serves as a high-resolution model to represent the KDM4 subfamily in crystallographic studies, are examined. Similar to previously reported inhibitors, the compounds described herein are competitors for the natural KDM4 cofactor, 2-oxoglutarate. The tetrazolylhydrazide scaffold fills an important gap in KDM4 inhibition and newly described, detailed interactions of inhibitor moieties pave the way to the development of compounds with high target-binding affinity and increased membrane permeability, at the same time.

PubMed: 31475772
DOI: 10.1002/cmdc.201900441

実験手法

X-RAY DIFFRACTION (1.333 Å)