Expanding Cofactor Repertoire of Protein Lysine Methyltransferase for Substrate Labeling
- 15 April 2011
- journal article
- letter
- Published by American Chemical Society (ACS) in ACS Chemical Biology
- Vol. 6 (7), 679-684
- https://doi.org/10.1021/cb2000567
Abstract
Protein lysine methyltransferases (PKMTs) play crucial roles in normal physiology and disease processes. Profiling PKMT targets is an important but challenging task. With cancer-relevant G9a as a target, we have demonstrated success in developing S-adenosyl-l-methionine (SAM) analogues, particularly (E)-hex-2-en-5-ynyl SAM (Hey-SAM), as cofactors for engineered G9a. Hey-SAM analogue in combination with G9a Y1154A mutant modifies the same set of substrates as their native counterparts with remarkable efficiency. (E)-Hex-2-en-5-ynylated substrates undergo smooth click reaction with an azide-based probe. This approach is thus suitable for substrate characterization of G9a and expected to further serve as a starting point to evolve other PKMTs to utilize a similar set of cofactors.Keywords
This publication has 34 references indexed in Scilit:
- Palmitoylome profiling reveals S-palmitoylation–dependent antiviral activity of IFITM3Nature Chemical Biology, 2010
- Histone methyltransferases in cancerSeminars in Cell & Developmental Biology, 2010
- Chemical mechanisms of histone lysine and arginine modificationsBiochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 2008
- Protein lysine methyltransferase G9a acts on non-histone targetsNature Chemical Biology, 2008
- Modulation of p53 Function by SET8-Mediated Methylation at Lysine 382Molecular Cell, 2007
- Synthesis of S-adenosyl-L-methionine analogs and their use for sequence-specific transalkylation of DNA by methyltransferasesNature Protocols, 2006
- 5-Aza-2′-deoxycytidine-mediated reductions in G9A histone methyltransferase and histone H3 K9 di-methylation levels are linked to tumor suppressor gene reactivationOncogene, 2006
- The SET domain protein Metnase mediates foreign DNA integration and links integration to nonhomologous end-joining repairProceedings of the National Academy of Sciences, 2005
- The many faces of histone lysine methylationCurrent Opinion in Cell Biology, 2002
- Allele-specific activators and inhibitors for kinesinProceedings of the National Academy of Sciences, 1999