6t1n
From Proteopedia
Crystal structure of MLLT1 (ENL) YEATS domain in complexed with benzimidazole-amide derivative 5
Structural highlights
DiseaseENL_HUMAN A chromosomal aberration involving MLLT1 is associated with acute leukemias. Translocation t(11;19)(q23;p13.3) with KMT2A/MLL1. The result is a rogue activator protein. FunctionENL_HUMAN Component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA.[1] [2] Publication Abstract from PubMedYEATS-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. Structural Insights into Interaction Mechanisms of Alternative Piperazine-urea YEATS Domain Binders in MLLT1.,Ni X, Heidenreich D, Christott T, Bennett J, Moustakim M, Brennan PE, Fedorov O, Knapp S, Chaikuad A ACS Med Chem Lett. 2019 Nov 25;10(12):1661-1666. doi:, 10.1021/acsmedchemlett.9b00460. eCollection 2019 Dec 12. PMID:31857843[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
