Analysis of p300/CBP histone acetyltransferase regulation using circular permutation and semisynthesis

Kannan R. Karukurichi, Ling Wang, Lerna Uzasci, Cara Marie Manlandro, Qing Wang, Philip A. Cole

Research output: Contribution to journalArticlepeer-review

Abstract

(Chemical Equation Presented) The histone acetyltransferase (HAT) p300/CBP has been shown to undergo autoacetylation on lysines in an apparent regulatory loop that stimulates HAT activity. Here we have developed a strategy to introduce acetyl-Lys at up to six known modification sites in p300/CBP HAT using a combination of circular permutation and expressed protein ligation. We show that these semisynthetic, circularly permuted acetylated proteins retain high affinity for an acetyl-CoA substrate analogue and that HAT activity correlates positively with degree of acetylation. This study provides novel evidence for control of p300/CBP HAT activity by site-specific autoacetylation and outlines a potentially general strategy for using expressed protein ligation and circular permutation to chemically interrogate internal regions of proteins.

Original languageEnglish (US)
Pages (from-to)1222-1223
Number of pages2
JournalJournal of the American Chemical Society
Volume132
Issue number4
DOIs
StatePublished - Feb 3 2010

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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