6FUK

Crystal structure of UTX complexed with 5-carboxy-8-hydroxyquinoline

6FUK の概要

• エントリーDOI: 10.2210/pdb6fuk/pdb
• 分子名称: Lysine-specific demethylase 6A, MANGANESE (II) ION, 8-hydroxyquinoline-5-carboxylic acid, ... (8 entities in total)
• 機能のキーワード: jumonji demethylase, inhibitor, 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: 61098.40

構造登録者

Esposito, C.,Sledz, P.,Caflisch, A. (登録日: 2018-02-27, 公開日: 2018-10-10, 最終更新日: 2024-01-17)

主引用文献

Esposito, C.,Wiedmer, L.,Caflisch, A.
In Silico Identification of JMJD3 Demethylase Inhibitors.
J Chem Inf Model, 58:2151-2163, 2018

PubMed Abstract: In the search for new demethylase inhibitors, we have developed a multistep protocol for in silico screening. Millions of poses generated by high-throughput docking or a 3D-pharmacophore search are first minimized by a classical force field and then filtered by semiempirical quantum mechanical calculations of the interaction energy with a selected set of functional groups in the binding site. The final ranking includes solvation effects which are evaluated in the continuum dielectric approximation (finite-difference Poisson equation). Application of the multistep protocol to JMJD3 jumonji demethylase has resulted in a dozen low-micromolar inhibitors belonging to five different chemical classes. We have solved the crystal structure of JMJD3 inhibitor 8 in the complex with UTX (a demethylase in the same subfamily as JMJD3) which validates the predicted binding mode. Compound 8 is a promising candidate for future optimization as it has a favorable ligand efficiency of 0.32 kcal/mol per nonhydrogen atom.

PubMed: 30226987
DOI: 10.1021/acs.jcim.8b00539

実験手法

X-RAY DIFFRACTION (2 Å)