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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.

SUBMITTER: Islam K

PROVIDER: S-EPMC3137739 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Expanding cofactor repertoire of protein lysine methyltransferase for substrate labeling.

Islam Kabirul K Zheng Weihong W Yu Haiqiang H Deng Haiteng H Luo Minkui M

ACS chemical biology 20110422 7

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 remark ...[more]

PMID: 21495674

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