Analysis of p300/CBP Histone Acetyltransferase Regulation Using Circular Permutation and Semisynthesis

被引：18

作者：

Karukurichi, Kannan R. ^{[1
]}

Wang, Ling ^{[1
]}

Uzasci, Lerna ^{[1
]}

Manlandro, Cara Marie ^{[1
]}

Wang, Qing ^{[1
]}

Cole, Philip A. ^{[1
]}

机构：

[1] Johns Hopkins Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2010年 / 132卷 / 04期

关键词：

RECOMBINANT PROTEINS; ACETYLATION; LIGATION; DOMAIN; HAT;

D O I：

10.1021/ja909466d

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The histone acetyltransferase (HAT) p300/CBP has been shown to undergo autoacetylation on lysines in an apparent regulatory loop that stimulations HAT activity. Here we have developed a strategy to introduce acetyl-Lys at Lip 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.

引用

页码：1222 / +

页数：4

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