6T1N

Crystal structure of MLLT1 (ENL) YEATS domain in complexed with benzimidazole-amide derivative 5

Summary for 6T1N

• Entry DOI: 10.2210/pdb6t1n/pdb
• Descriptor: Protein ENL, 4-chloranyl-~{N}-[2-(piperidin-1-ylmethyl)-3~{H}-benzimidazol-5-yl]benzamide, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: transcription, yeats domain, enl, mllt1, chemical probe, inhibitor, structural genomics, structural genomics consortium, sgc
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 19028.34

Authors

Chaikuad, A.,Heidenreich, D.,Moustakim, M.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Fedorov, O.,Brennan, P.E.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2019-10-04, release date: 2019-11-06, Last modification date: 2024-01-24)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.95 Å)