A Genetically Encoded Allysine for the Synthesis of Proteins with Site-Specific Lysine Dimethylation

Zhipeng A. Wang, Yu Zeng, Yadagiri Kurra, Xin Wang, Jeffery M. Tharp, Erol C. Vatansever, Willie Hsu, Susie Dai, Xinqiang Fang, Wenshe R. Liu

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Using the amber suppression approach, Nϵ-(4-azidobenzoxycarbonyl)-δ,ϵ-dehydrolysine, an allysine precursor is genetically encoded in E. coli. Its genetic incorporation followed by two sequential biocompatible reactions allows convenient synthesis of proteins with site-specific lysine dimethylation. Using this approach, dimethyl-histone H3 and p53 proteins have been synthesized and used to probe functions of epigenetic enzymes including histone demethylase LSD1 and histone acetyltransferase Tip60. We confirmed that LSD1 is catalytically active toward H3K4me2 and H3K9me2 but inert toward H3K36me2, and methylation at p53 K372 directly activates Tip60 for its catalyzed acetylation at p53 K120.

Original languageEnglish (US)
Pages (from-to)212-216
Number of pages5
JournalAngewandte Chemie - International Edition
Volume56
Issue number1
DOIs
StatePublished - 2017
Externally publishedYes

Fingerprint

Lysine
Histone Demethylases
Amber
Proteins
Histone Acetyltransferases
Acetylation
Methylation
Histones
Escherichia coli
Enzymes
allysine
dehydrolysine

Keywords

  • allysine
  • amber suppression
  • dimethyllysine
  • genetic code expansion
  • lysine dimethylation

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

Cite this

Wang, Z. A., Zeng, Y., Kurra, Y., Wang, X., Tharp, J. M., Vatansever, E. C., ... Liu, W. R. (2017). A Genetically Encoded Allysine for the Synthesis of Proteins with Site-Specific Lysine Dimethylation. Angewandte Chemie - International Edition, 56(1), 212-216. https://doi.org/10.1002/anie.201609452

A Genetically Encoded Allysine for the Synthesis of Proteins with Site-Specific Lysine Dimethylation. / Wang, Zhipeng A.; Zeng, Yu; Kurra, Yadagiri; Wang, Xin; Tharp, Jeffery M.; Vatansever, Erol C.; Hsu, Willie; Dai, Susie; Fang, Xinqiang; Liu, Wenshe R.

In: Angewandte Chemie - International Edition, Vol. 56, No. 1, 2017, p. 212-216.

Research output: Contribution to journalArticle

Wang, ZA, Zeng, Y, Kurra, Y, Wang, X, Tharp, JM, Vatansever, EC, Hsu, W, Dai, S, Fang, X & Liu, WR 2017, 'A Genetically Encoded Allysine for the Synthesis of Proteins with Site-Specific Lysine Dimethylation', Angewandte Chemie - International Edition, vol. 56, no. 1, pp. 212-216. https://doi.org/10.1002/anie.201609452
Wang, Zhipeng A. ; Zeng, Yu ; Kurra, Yadagiri ; Wang, Xin ; Tharp, Jeffery M. ; Vatansever, Erol C. ; Hsu, Willie ; Dai, Susie ; Fang, Xinqiang ; Liu, Wenshe R. / A Genetically Encoded Allysine for the Synthesis of Proteins with Site-Specific Lysine Dimethylation. In: Angewandte Chemie - International Edition. 2017 ; Vol. 56, No. 1. pp. 212-216.
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