Dual Genetic Encoding of Acetyl‐lysine and Non‐deacetylatable Thioacetyl‐lysine Mediated by Flexizyme

Abstract

Acetylation of lysine residues is an important post‐translational protein modification. Lysine acetylation in histones and its crosstalk with other post‐translational modifications in histone and non‐histone proteins are crucial to DNA replication, DNA repair, and transcriptional regulation. We incorporated acetyl‐lysine (AcK) and the non‐hydrolyzable thioacetyl‐lysine (ThioAcK) into full‐length proteins in vitro, mediated by flexizyme. ThioAcK and AcK were site‐specifically incorporated at different lysine positions into human histone H3, either individually or in pairs. We demonstrate that the thioacetyl group in histone H3 could not be removed by the histone deacetylase sirtuin type 1. This method provides a powerful tool to study protein acetylation and its role in crosstalk between post‐translational modifications.

Document Details

Document Type
Pub Defense Publication
Publication Date
Feb 23, 2016
Source ID
10.1002/anie.201511750

Entities

People

  • Chenguang Fan
  • Denton Hoyer
  • Dieter Söll
  • Hai Xiong
  • Markus Englert
  • Noah M. Reynolds
  • Scott J. Miller

Organizations

  • Defense Advanced Research Projects Agency
  • National Institutes of Health
  • Yale University

Tags

Fields of Study

  • Biology
  • Computer science

Readers

  • Clinical Trial Research.
  • Molecular Biology and Genetics

Technology Areas

  • Biotechnology