Expanding cofactor repertoire of protein lysine methyltransferase for substrate labeling Journal Article

   


Authors: Islam, K.; Zheng, W.; Yu, H.; Deng, H.; Luo, M.
Article 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. © 2011 American Chemical Society.
Keywords: mutation; methyltransferase; histone-lysine n-methyltransferase; chemical structure; chemical reaction; synthesis; lysine; coenzymes; s-adenosylmethionine; s adenosylmethionine; histocompatibility antigens; azide
Journal Title: ACS Chemical Biology
Volume: 6
Issue: 7
ISSN: 1554-8929
Publisher: American Chemical Society  
Date Published: 2011-07-15
Start Page: 679
End Page: 684
Language: English
DOI: 10.1021/cb2000567
PROVIDER: scopus
PMCID: PMC3137739
PUBMED: 21495674
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-79960496067&partnerID=40&md5=cd0ecb20226c0809f675f928e96a5875
Notes: --- - "Export Date: 17 August 2011" - "Source: Scopus"
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MSK Authors
  1. Weihong Zheng
    11 Zheng
  2. Minkui Luo
    70 Luo
  3. Kabirul Islam
    9 Islam
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