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 journalArticle

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

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Histone Acetyltransferases
Proteins
Ligation
Acetylation
Acetyl Coenzyme A
Lysine
Substrates

ASJC Scopus subject areas

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

Cite this

Analysis of p300/CBP histone acetyltransferase regulation using circular permutation and semisynthesis. / Karukurichi, Kannan R.; Wang, Ling; Uzasci, Lerna; Manlandro, Cara Marie; Wang, Qing; Cole, Philip A.

In: Journal of the American Chemical Society, Vol. 132, No. 4, 03.02.2010, p. 1222-1223.

Research output: Contribution to journalArticle

Karukurichi, Kannan R. ; Wang, Ling ; Uzasci, Lerna ; Manlandro, Cara Marie ; Wang, Qing ; Cole, Philip A. / Analysis of p300/CBP histone acetyltransferase regulation using circular permutation and semisynthesis. In: Journal of the American Chemical Society. 2010 ; Vol. 132, No. 4. pp. 1222-1223.
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