6U9K

MLL1 SET N3861I/Q3867L bound to inhibitor 18 (TC-5153)

6U9K の概要

• エントリーDOI: 10.2210/pdb6u9k/pdb
• 分子名称: Histone-lysine N-methyltransferase, ZINC ION, 5'-([(3S)-3-amino-3-carboxypropyl]{[1-(3,3-diphenylpropyl)azetidin-3-yl]methyl}amino)-5'-deoxyadenosine, ... (5 entities in total)
• 機能のキーワード: transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 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: 37970.78

構造登録者

Petrunak, E.M.,Stuckey, J.A. (登録日: 2019-09-09, 公開日: 2020-07-01, 最終更新日: 2023-10-11)

主引用文献

Chern, T.R.,Liu, L.,Petrunak, E.,Stuckey, J.A.,Wang, M.,Bernard, D.,Zhou, H.,Lee, S.,Dou, Y.,Wang, S.
Discovery of Potent Small-Molecule Inhibitors of MLL Methyltransferase.
Acs Med.Chem.Lett., 11:1348-1352, 2020

PubMed Abstract: The mixed-lineage leukemia (MLL) protein, also known as MLL1, is a lysine methyltransferase specifically responsible for methylation of histone 3 lysine 4. MLL has been pursued as an attractive therapeutic target for the treatment of acute leukemia carrying the MLL fusion gene or MLL leukemia. Herein, we report the design, synthesis, and evaluation of an -adenosylmethionine-based focused chemical library which led to the discovery of potent small-molecule inhibitors directly targeting the MLL SET domain. Determination of cocrystal structures for a number of these MLL inhibitors reveals that they adopt a unique binding mode that locks the MLL SET domain in an open, inactive conformation.

PubMed: 32551023
DOI: 10.1021/acsmedchemlett.0c00229

実験手法

X-RAY DIFFRACTION (2 Å)