Structural insights into interaction mechanisms of alternative piperazine-urea YEATS domain binders in MLLT1

  • 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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Metadaten
Author:Xiaomin NiORCiDGND, David Jonas HeidenreichORCiDGND, Thomas Christott, James BennettORCiD, Moses MoustakimORCiD, Paul E. BrennanORCiD, Oleg FedorovORCiD, Stefan KnappORCiD, Apirat ChaikuadORCiD
URN:urn:nbn:de:hebis:30:3-726581
DOI:https://doi.org/10.1101/836932
Parent Title (English):bioRxiv
Document Type:Preprint
Language:English
Date of Publication (online):2019/11/09
Date of first Publication:2019/11/09
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/06/22
Issue:836932
Page Number:11
HeBIS-PPN:509407897
Institutes:Biochemie, Chemie und Pharmazie
Fachübergreifende Einrichtungen / Buchmann Institut für Molekulare Lebenswissenschaften (BMLS)
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International