Work

Expanding Cofactor Repertoire of Protein Lysine Methyltransferase for Substrate Labeling

Year: 2011

Type: article

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.

Source: ACS Chemical Biology

DOI: 10.1021/cb2000567

Authors: Kabirul Islam, Weihong Zheng, Haiqiang Yu, Haiteng Deng, Minkui Luo

Institutions: Memorial Sloan Kettering Cancer Center, Rockefeller University, Tsinghua University

Language: English

Topic: Click Chemistry and Applications

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: V Foundation for Cancer Research, National Institutes of Health, National Institute of General Medical Sciences

Awards: Enzyme-engineering Approaches to Dissect Protein Methylation Profiles, Profile substrates and inhibitors of protein lysine methyltransferase