Details

Project TitleA CHEMICAL BIOLOGY METHOD FOR THE SYNTHESIS OF PROTEIN SITE-SPECIFICALLY WITH LYSINE METHYLATION
Track CodeTAMU4583
Short DescriptionNone
Abstract

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A CHEMICAL BIOLOGY METHOD FOR THE SYNTHESIS OF PROTEIN SITE-SPECIFICALLY WITH LYSINE METHYLATION

Overview

Protein lysine methylation is a wide spread posttranslational modification in mammalian cells that regulates epigenetic functions of proteins. However, there is a lack of a straightforward approach for the synthesis of proteins with lysine methylation.



		TAMU 4583 Technology Picture

Technology

Using an evolved pyrrolysyl-tRNA synthetase and its cognate amber suppressor tRNAPyl, a precursor noncanonical amino acid is genetically encoded in E. coli by amber codon. Through simple mutagenesis to introduce amber mutation at a specific amino acid coding site in a protein coding gene and expression of this mutant protein in E. coli that codes our evolved pyrrolysyl-tRNA synthetase and tRNAPyl in the presence of our noncanonical amino acid, a mutant protein that can be further converted to a protein with site-specific lysine mono- or dimethylation can be synthesized

Advantages

  • Both mono- and dimethylation of lysine can be selectively installed in proteins.
  • There is no limitation on sites that can be installed with lysine methylation. Technically, any protein surface residues can be site-selectively mutated to be the one with lysine methylation.
  • Proteins are expressed in E. coli. Large quantities can be easily obtained.
  • The chemical processing to install lysine methylation is very simple which can achieve quantitation easily.
  • The developed approach is applicable to all proteins that can be expressed in E. coli.

Applications

  • The invention can be applied to synthesize mono- and dimethylated histones that are expensive commercial products for use in both academic research and industrial drug discovery
  • Further application of synthesized methyl-histones can be applied to synthesize methyl-nucleosomes that are hardly accessible and presumably expensive for researchers in both academia and industry
  • The invention can also be applied to synthesize other high interesting methylated proteins such as p53 as commercial products

Stage of Development

  • The invention has been finalized.

Lead Inventors

    Wenshe Liu, Ph.D.
    Department of Chemistry

Patent Status

    Patent Pending

For licensing information, please contact:


Shyamala Rajagopalan, Ph.D.
Licensing Associate
Texas A&M Technology Commercialization
srajagopalan@tamu.edu
(979) 862-3002
Docket: TAMU 4583

 
Tagsmethylation, protein, site-specific, lysine, histones
 
Posted DateApr 19, 2017 11:27 AM

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