Structure-based approach toward identification of inhibitory fragments for eleven-nineteen-leukemia protein (ENL)

Structure-based approach toward identification of inhibitory fragments for eleven-nineteen-leukemia protein (ENL)

Lysine acetylation is an epigenetic mark that is principally recognized by bromodomains, and recently structurally diverse YEATS domains also emerged as readers of lysine acetyl/acylations. Here we present a crystallography-based strategy and the discovery of fragments binding to the ENL YEATS domai...

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Bibliographic Details
Main Authors: Heidenreich, D, Moustakim, M, Schmidt, J, Merk, D, Brennan, P, Fedorov, O, Chaikuad, A, Knapp, S
Format: Journal article
Language:English
Published: American Chemical Society 2018
Description
Summary:Lysine acetylation is an epigenetic mark that is principally recognized by bromodomains, and recently structurally diverse YEATS domains also emerged as readers of lysine acetyl/acylations. Here we present a crystallography-based strategy and the discovery of fragments binding to the ENL YEATS domain, a potential drug target. Crystal structures combined with synthetic efforts led to the identification of a submicromolar binder, providing first starting points for the development of chemical probes for this reader domain family.

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