Chemical basis for the recognition of trimethyllysine by epigenetic reader proteins.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 26578293.
- Also identified by DOI 10.1038/ncomms9911 and PMC identifier 4673829.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Acetyltransferases
- Antigens, Nuclear
- Histones
- Jumonji Domain-Containing Histone Demethylases
- Lysine
- Nerve Tissue Proteins
- Retinoblastoma-Binding Protein 2
- Transcription Factor TFIID
- Transcription Factors