8Z7C

Structure of G9a in complex with compound 7i

これはPDB形式変換不可エントリーです。

8Z7C の概要

• エントリーDOI: 10.2210/pdb8z7c/pdb
• 分子名称: Histone-lysine N-methyltransferase EHMT2, ZINC ION, SINEFUNGIN, ... (5 entities in total)
• 機能のキーワード: histone lysine methyltransferase, inhibitor, protein-inhibitor complex, transferase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 67541.25

構造登録者

Niwa, H.,Shirai, F.,Sato, S.,Nishigaya, Y.,Ihara, K.,Shirouzu, M.,Umehara, T. (登録日: 2024-04-20, 公開日: 2025-01-22)

主引用文献

Nishigaya, Y.,Takase, S.,Sumiya, T.,Sato, T.,Niwa, H.,Sato, S.,Nakata, A.,Matsuoka, S.,Maemoto, Y.,Hashimoto, N.,Namie, R.,Honma, T.,Umehara, T.,Shirouzu, M.,Koyama, H.,Yoshida, M.,Ito, A.,Shirai, F.
Structure-based development of novel substrate-type G9a inhibitors as epigenetic modulators for sickle cell disease treatment.
Bioorg.Med.Chem.Lett., 110:129856-129856, 2024

PubMed Abstract: The discovery and development of structurally distinct lysine methyltransferase G9a inhibitors have been the subject of intense research in epigenetics. Structure-based optimization was conducted, starting with the previously reported seed compound 7a and lead to the identification of a highly potent G9a inhibitor, compound 7i (IC = 0.024 μM). X-ray crystallography for the ligand-protein interaction and kinetics study, along with surface plasmon resonance (SPR) analysis, revealed that compound 7i interacts with G9a in a unique binding mode. In addition, compound 7i caused attenuation of cellular H3K9me2 levels and induction of γ-globin mRNA expression in HUDEP-2 cells in a dose-dependent manner.

PubMed: 38914346
DOI: 10.1016/j.bmcl.2024.129856

実験手法

X-RAY DIFFRACTION (1.52 Å)