Se-adenosyl-L-selenomethionine cofactor analogue as a reporter of protein methylation Journal Article

   


Authors: Bothwell, I. R.; Islam, K.; Chen, Y.; Zheng, W.; Blum, G.; Deng, H.; Luo, M.
Article Title: Se-adenosyl-L-selenomethionine cofactor analogue as a reporter of protein methylation
Abstract: Posttranslational methylation by S-adenosyl-l-methionine(SAM)-dependent methyltransferases plays essential roles in modulating protein function in both normal and disease states. As such, there is a growing need to develop chemical reporters to examine the physiological and pathological roles of protein methyltransferases. Several sterically bulky SAM analogues have previously been used to label substrates of specific protein methyltransferases. However, broad application of these compounds has been limited by their general incompatibility with native enzymes. Here we report a SAM surrogate, ProSeAM (propargylic Se-adenosyl-l-selenomethionine), as a reporter of methyltransferases. ProSeAM can be processed by multiple protein methyltransferases for substrate labeling. In contrast, sulfur-based propargylic SAM undergoes rapid decomposition at physiological pH, likely via an allene intermediate. In conjunction with fluorescent/affinity-based azide probes, copper-catalyzed azide-alkyne cycloaddition chemistry, in-gel fluorescence visualization and proteomic analysis, we further demonstrated ProSeAM's utility to profile substrates of endogenous methyltransferases in diverse cellular contexts. These results thus feature ProSeAM as a convenient probe to study the activities of endogenous protein methyltransferases. © 2012 American Chemical Society.
Keywords: controlled study; protein expression; unclassified drug; human cell; methylation; chemical analysis; proteins; enzyme inhibition; enzyme degradation; fluorescence; fluorescent dye; ph; cancer cell culture; in vitro study; enzyme activity; enzyme substrate; cell line, tumor; proteomics; physiology; methyltransferases; protein processing; colon cancer; histone h3; binding site; probes; models, molecular; molecular structure; high performance liquid chromatography; alkylation; catalysis; amino acids; protein structure; visualization; copper; lysine; cysteine; substrates; hydrogen-ion concentration; enzyme mechanism; protein methylation; cycloaddition; selenomethionine; cofactors; enzyme stability; hek293 cells; protein methyltransferase; s adenosylhomocysteine; acetylene; allene derivative; proteomic analysis; azide-alkyne cycloaddition; sulfur; disease state; label substrates; s adenosyl l methionines; broad application; cellular contexts; native enzymes; physiological ph; protein functions; rapid decomposition; selenium compounds; propargylic se adenosyl levo selenomethionine; decomposition
Journal Title: Journal of the American Chemical Society
Volume: 134
Issue: 36
ISSN: 0002-7863
Publisher: American Chemical Society  
Date Published: 2012-09-12
Start Page: 14905
End Page: 14912
Language: English
DOI: 10.1021/ja304782r
PROVIDER: scopus
PMCID: PMC3458307
PUBMED: 22917021
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-84866414211&partnerID=40&md5=d41bf7be3022c95e836c0eba77a40879
Notes: --- - "Export Date: 1 October 2012" - "CODEN: JACSA" - "Source: Scopus"
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MSK Authors
  1. Weihong Zheng
    11 Zheng
  2. Minkui Luo
    70 Luo
  3. Kabirul Islam
    9 Islam
  4. Gil Blum
    15 Blum
  5. Ian Bothwell
    8 Bothwell
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