Molecular Recognition of Methacryllysine and Crotonyllysine by the AF9 YEATS Domain

Nurgül Bilgin, Laust Moesgaard, Mohammad M. Rahman, Vildan A. Türkmen, Jacob Kongsted*, Jasmin Mecinović

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Histone lysine methacrylation and crotonylation are epigenetic marks that play important roles in human gene regulation. Here, we explore the molecular recognition of histone H3 peptides possessing methacryllysine and crotonyllysine at positions 18 and 9 (H3K18 and H3K9) by the AF9 YEATS domain. Our binding studies demonstrate that the AF9 YEATS domain displays a higher binding affinity for histones possessing crotonyllysine than the isomeric methacryllysine, indicating that AF9 YEATS distinguishes between the two regioisomers. Molecular dynamics simulations reveal that the crotonyllysine/methacryllysine-mediated desolvation of the AF9 YEATS domain provides an important contribution to the recognition of both epigenetic marks. These results provide important knowledge for the development of AF9 YEATS inhibitors, an area of biomedical interest.
Original languageEnglish
Article number7002
JournalInternational Journal of Molecular Sciences
Volume24
Issue number8
Number of pages10
ISSN1422-0067
DOIs
Publication statusPublished - 2023

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