title: 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.
authors.forename: Kabirul
authors.initials: K
authors.lastname: Islam
authors.forename: Weihong
authors.initials: W
authors.lastname: Zheng
authors.forename: Haiqiang
authors.initials: H
authors.lastname: Yu
authors.forename: Haiteng
authors.initials: H
authors.lastname: Deng
authors.forename: Minkui
authors.initials: M
authors.lastname: Luo
mesh_terms: D003067:Coenzymes / Q000737:chemistry* / Q000378:metabolism; D006649:Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D012436:S-Adenosylmethionine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D003067:Coenzymes; D006649:Histocompatibility Antigens; D012436:S-Adenosylmethionine; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase