Labeling substrates of protein arginine methyltransferase with engineered enzymes and matched S-adenosyl-l-methionine analogues Journal Article
| Authors: | Wang, R.; Zheng, W.; Yu, H.; Deng, H.; Luo, M. |
| Article Title: | Labeling substrates of protein arginine methyltransferase with engineered enzymes and matched S-adenosyl-l-methionine analogues |
| Abstract: | Elucidating physiological and pathogenic functions of protein methyltransferases (PMTs) relies on knowing their substrate profiles. S-adenosyl-l-methionine (SAM) is the sole methyl-donor cofactor of PMTs. Recently, SAM analogues have emerged as novel small-molecule tools to efficiently label PMT substrates. Here we reported the development of a clickable SAM analogue cofactor, 4-propargyloxy-but-2-enyl SAM, and its implementation to label substrates of human protein arginine methyltransferase 1 (PRMT1). In the system, the SAM analogue cofactor, coupled with matched PRMT1 mutants rather than native PRMT1, was shown to label PRMT1 substrates. The transferable 4-propargyloxy-but-2-enyl moiety of the SAM analogue further allowed corresponding modified substrates to be characterized through a subsequent click chemical ligation with an azido-based probe. The SAM analogue, in combination with a rational protein-engineering approach, thus shows potential to label and identify PMT targets in the context of a complex cellular mixture. © 2011 American Chemical Society. |
| Journal Title: | Journal of the American Chemical Society |
| Volume: | 133 |
| Issue: | 20 |
| ISSN: | 0002-7863 |
| Publisher: | American Chemical Society |
| Date Published: | 2011-05-25 |
| Start Page: | 7648 |
| End Page: | 7651 |
| Language: | English |
| DOI: | 10.1021/ja2006719 |
| PROVIDER: | scopus |
| PUBMED: | 21539310 |
| PMCID: | PMC3104021 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 23 June 2011" - "CODEN: JACSA" - "Source: Scopus" |
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