3JRX

Crystal structure of the BC domain of ACC2 in complex with soraphen A

3JRX の概要

• エントリーDOI: 10.2210/pdb3jrx/pdb
• 関連するPDBエントリー: 2HJW 3JRW
• 分子名称: Acetyl-CoA carboxylase 2, SORAPHEN A (3 entities in total)
• 機能のキーワード: bc domain, soraphen a, alternative splicing, atp-binding, biotin, fatty acid biosynthesis, ligase, lipid synthesis, manganese, membrane, metal-binding, multifunctional enzyme, nucleotide-binding, phosphoprotein, polymorphism
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endomembrane system: O00763
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 65943.96

構造登録者

Cho, Y.S.,Lee, J.I.,Shin, D.,Kim, H.T.,Lee, T.G.,Heo, Y.S. (登録日: 2009-09-09, 公開日: 2010-01-12, 最終更新日: 2023-11-01)

主引用文献

Cho, Y.S.,Lee, J.I.,Shin, D.,Kim, H.T.,Jung, H.Y.,Lee, T.G.,Kang, L.W.,Ahn, Y.J.,Cho, H.S.,Heo, Y.S.
Molecular mechanism for the regulation of human ACC2 through phosphorylation by AMPK.
Biochem.Biophys.Res.Commun., 391:187-192, 2010

PubMed Abstract: 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.

PubMed: 19900410
DOI: 10.1016/j.bbrc.2009.11.029

実験手法

X-RAY DIFFRACTION (2.5 Å)