Investigating d-lysine stereochemistry for epigenetic methylation, demethylation and recognition.
journal contributionposted on 2019-06-14, 11:42 authored by R Belle, AHK Al Temimi, K Kumar, BJGE Pieters, A Tumber, JE Dunford, C Johansson, U Oppermann, T Brown, CJ Schofield, RJ Hopkinson, RS Paton, A Kawamura, J Mecinović
Histone lysine methylation is regulated by Nε-methyltransferases, demethylases, and Nε-methyl lysine binding proteins. Thermodynamic, catalytic and computational studies were carried out to investigate the interaction of three epigenetic protein classes with synthetic histone substrates containing l- and d-lysine residues. The results reveal that out of the three classes, Nε-methyl lysine binding proteins are superior in accepting lysines with the d-configuration.
This work was supported by the ERC Starting Grant to J. M. (ChemEpigen-715691) and to A. K. (EPITOOLS-679479), the Netherlands Organization for Scientific Research (NCI-TA 731.015.202), Royal Society Dorothy Hodgkin Fellowship (A. K.), the Wellcome Trust, Cancer Research UK, the Engineering & Physical Sciences Research Council UK, the John Fell Oxford University Press (OUP) Research Fund, and the NIHR Oxford Biomedical Research Unit. We gratefully acknowledge Dr D. McClymont for his support in developing the Matlab script.
CitationChemical Communications, 2017, 53 (99), pp. 13264-13267
Author affiliation/Organisation/COLLEGE OF SCIENCE AND ENGINEERING/Department of Chemistry
- AM (Accepted Manuscript)