Molecular mechanism for the regulation of human ACC2 through phosphorylation by AMPK

被引：66

作者：

Cho, Yong Soon ^{[2
,3
]}

Lee, Jae Il ^{[2
]}

Shin, Dongkyu ^{[2
]}

Kim, Hyun Tae ^{[2
]}

Jung, Ha Yun ^{[1
]}

Lee, Tae Gyu ^{[2
]}

Kang, Lin-Woo ^{[4
]}

Ahn, Yeh-Jin ^{[5
]}

Cho, Hyun-Soo ^{[3
]}

Heo, Yong-Seok ^{[1
]}

机构：

[1] Konkuk Univ, Dept Chem, Seoul 143701, South Korea

[2] CrystalGenomics Inc, R&D Ctr, Seoul 138739, South Korea

[3] Yonsei Univ, Dept Biol, Coll Life Sci & Biotechnol, Seoul 120749, South Korea

[4] Konkuk Univ, Dept Adv Technol Fus, Seoul 143701, South Korea

[5] Sangmyung Univ, Coll Nat Sci, Dept Life Sci, Seoul 110743, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2010年 / 391卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

Acetyl-CoA carboxylase (ACC); Biotin carboxylase (BC); Fatty acid metabolism; AMP-activated protein kinase (AMPK); Phosphorylation; Short-term regulation; Soraphen A; Crystal structure; ACETYL-COA CARBOXYLASE; COENZYME-A CARBOXYLASE; FATTY-ACID SYNTHESIS; BIOTIN CARBOXYLASE; CRYSTAL-STRUCTURE; SUBUNIT; DOMAIN; PURIFICATION; EXPRESSION;

D O I：

10.1016/j.bbrc.2009.11.029

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Acetyl-CoA carboxylases (ACCs) have been highlighted as therapeutic targets for obesity and diabetes. as they play Crucial roles in fatty acid metabolism. ACC activity is regulated through the short-term mechanism of inactivation by reversible phosphorylation. Here. we report the crystal structures of the biotin carboxylase (BC) domain of human ACC2 phosphorylated by AMP-activated protein kinase (AMPK) The phosphorylated Ser222 binds to the putative dimer interface of BC. disrupting polymerization and providing the molecular mechanism of inactivation by AMPK. We also determined the Structure of the human BC domain in complex with soraphen A, a macrocyclic polyketide natural product This Structure shows that the compound binds to the binding site of phosphorylated Ser222. implying that its inhibition mechanism is the same as that of phosphorylation by AMPK (c) 2009 Elsevier Inc. All rights reserved.

引用

页码：187 / 192

页数：6

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