6T1J

Crystal structure of MLLT1 (ENL) YEATS domain in complexed with piperazine-urea derivative 2

6T1J の概要

• エントリーDOI: 10.2210/pdb6t1j/pdb
• 分子名称: Protein ENL, 1,2-ETHANEDIOL, ~{N}-[[4-(pyrrolidin-1-ylmethyl)phenyl]methyl]-4-thiophen-2-ylcarbonyl-piperazine-1-carboxamide, ... (4 entities in total)
• 機能のキーワード: transcription, yeats domain, enl, mllt1, chemical probe, inhibitor, structural genomics, structural genomics consortium, sgc
• 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: 19072.03

構造登録者

Chaikuad, A.,Heidenreich, D.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Fedorov, O.,Knapp, S.,Structural Genomics Consortium (SGC) (登録日: 2019-10-04, 公開日: 2019-11-06, 最終更新日: 2024-01-24)

主引用文献

Ni, X.,Heidenreich, D.,Christott, T.,Bennett, J.,Moustakim, M.,Brennan, P.E.,Fedorov, O.,Knapp, S.,Chaikuad, A.
Structural Insights into Interaction Mechanisms of Alternative Piperazine-urea YEATS Domain Binders in MLLT1.
Acs Med.Chem.Lett., 10:1661-1666, 2019

PubMed Abstract: YEATS-domain-containing MLLT1 is an acetyl/acyl-lysine reader domain, which is structurally distinct from well-studied bromodomains and has been strongly associated in development of cancer. Here, we characterized piperazine-urea derivatives as an acetyl/acyl-lysine mimetic moiety for MLLT1. Crystal structures revealed distinct interaction mechanisms of this chemotype compared to the recently described benzimidazole-amide based inhibitors, exploiting different binding pockets within the protein. Thus, the piperazine-urea scaffold offers an alternative strategy for targeting the YEATS domain family.

PubMed: 31857843
DOI: 10.1021/acsmedchemlett.9b00460

実験手法

X-RAY DIFFRACTION (1.97 Å)