Chemical basis for the recognition of trimethyllysine by epigenetic reader proteins

Jos J.A.G. Kamps, Jiaxin Huang, Jordi Poater, Chao Xu, Bas J.G.E. Pieters, Aiping Dong, Jinrong Min, Woody Sherman, Thijs Beuming, F. Matthias Bickelhaupt, Haitao Li, Jasmin Mecinovi*

*Kontaktforfatter

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstract

A large number of structurally diverse epigenetic reader proteins specifically recognize methylated lysine residues on histone proteins. Here we describe comparative thermodynamic, structural and computational studies on recognition of the positively charged natural trimethyllysine and its neutral analogues by reader proteins. This work provides experimental and theoretical evidence that reader proteins predominantly recognize trimethyllysine via a combination of favourable cation-π interactions and the release of the high-energy water molecules that occupy the aromatic cage of reader proteins on the association with the trimethyllysine side chain. These results have implications in rational drug design by specifically targeting the aromatic cage of readers of trimethyllysine.

OriginalsprogEngelsk
Artikelnummer8911
TidsskriftNature Communications
Vol/bind6
ISSN2041-1723
DOI
StatusUdgivet - 18. nov. 2015
Udgivet eksterntJa

Fingeraftryk

Dyk ned i forskningsemnerne om 'Chemical basis for the recognition of trimethyllysine by epigenetic reader proteins'. Sammen danner de et unikt fingeraftryk.

Citationsformater