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bioRxiv · 10.1101/836932

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.·Fedorov, O.·Knapp, S.·Chaikuad, A.
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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.

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Ni, X., Heidenreich, D., Christott, T., Bennett, J., Moustakim, M., Brennan, P., Fedorov, O., Knapp, S., Chaikuad, A.. 2019-11-09. Structural insights into interaction mechanisms of alternative piperazine-urea YEATS domain binders in MLLT1. https://doi.org/10.1101/836932

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