ISDA: 6T1L

Deposition Date 2019-10-04

Release Date 2019-11-06

Last Version Date 2024-01-24

Entry Detail

PDB ID:

6T1L

Keywords:

TRANSCRIPTION

Title:

Crystal structure of MLLT1 (ENL) YEATS domain in complexed with piperazine-urea derivative 3

Biological Source:

Source Organism(s):

Homo sapiens (Taxon ID: 9606)

Expression System(s):

Escherichia coli bl21(de3)

Method Details:

Experimental Method:

X-RAY DIFFRACTION

Resolution:

2.00 Å

R-Value Free:

0.26

R-Value Work:

0.21

R-Value Observed:

0.22

Space Group:

P 43 21 2

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Macromolecular Entities

Structures with similar UniProt ID

Protein Blast

Polymer Type:polypeptide(L)
Molecule:Protein ENL
Gene (Uniprot):MLLT1
Chain IDs:A
Chain Length:154
Number of Molecules:1
Biological Source:Homo sapiens

UniProt ID:Q03111 Pfam ID:PF03366

Ligand Molecules

EDO

M7N

Primary Citation

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, P.E, Fedorov, O, Knapp, S, Chaikuad, A.Show

Acs Med.Chem.Lett. 10 1661 1666 (2019)

PMID: 31857843 DOI: 10.1021/acsmedchemlett.9b00460

Abstact

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.

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Primary Citation of related structures

Abstact

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