title: A Genetically Encoded Allysine for the Synthesis of Proteins with Site-Specific Lysine Dimethylation.
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.
authors.affiliation: Department of Chemistry, Texas A & M University, Corner of Ross and Spence Streets, College Station, TX 77843, USA.
authors.forename: Zhipeng A
authors.initials: ZA
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Texas A & M University, Corner of Ross and Spence Streets, College Station, TX 77843, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Chemistry, Texas A & M University, Corner of Ross and Spence Streets, College Station, TX 77843, USA.
authors.forename: Yadagiri
authors.initials: Y
authors.lastname: Kurra
authors.affiliation: Department of Plant Pathology and Microbiology, Institute for Plant Genomics, Office of the Taxes State Chemist, Department of Veterinary Pathobiology, College Station, TX, 77843, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Texas A & M University, Corner of Ross and Spence Streets, College Station, TX 77843, USA.
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Tharp
authors.affiliation: Department of Chemistry, Texas A & M University, Corner of Ross and Spence Streets, College Station, TX 77843, USA.
authors.forename: Erol C
authors.initials: EC
authors.lastname: Vatansever
authors.affiliation: Department of Chemistry, Texas A & M University, Corner of Ross and Spence Streets, College Station, TX 77843, USA.
authors.forename: Willie W
authors.initials: WW
authors.lastname: Hsu
authors.affiliation: Department of Plant Pathology and Microbiology, Institute for Plant Genomics, Office of the Taxes State Chemist, Department of Veterinary Pathobiology, College Station, TX, 77843, USA.
authors.forename: Susie
authors.initials: S
authors.lastname: Dai
authors.affiliation: Fujian Institute of Research on the Structure of Matter, Chinese Academy of Science, Fuzhou, Fujian, 350002, P.R. China.
authors.forename: Xinqiang
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Chemistry, Texas A & M University, Corner of Ross and Spence Streets, College Station, TX 77843, USA.
authors.forename: Wenshe R
authors.identifier: 0000-0002-7078-6534
authors.initials: WR
authors.lastname: Liu
mesh_terms: D015074:2-Aminoadipic Acid / Q000031:analogs & derivatives* / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics*; D005815:Genetic Code; D006657:Histones / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000235:genetics; D008745:Methylation; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed / Q000379:methods*; D011499:Protein Processing, Post-Translational; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics
chemical_list: D006657:Histones; D016159:Tumor Suppressor Protein p53; D015074:2-Aminoadipic Acid; C002194:dehydrolysine; C000061:allysine; D008239:Lysine
keywords: allysine; amber suppression; dimethyllysine; genetic code expansion; lysine dimethylation