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ACS Chem Biol. 2011 Jul 15;6(7):679-84. doi: 10.1021/cb2000567. Epub 2011 Apr 22.

Expanding cofactor repertoire of protein lysine methyltransferase for substrate labeling.

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.

PMID:
21495674
PMCID:
PMC3137739
DOI:
10.1021/cb2000567
[Indexed for MEDLINE]
Free PMC Article
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