1W93

Crystal Structure of Biotin Carboxylase Domain of Acetyl-Coenzyme A Carboxylase from Saccharomyces cerevisiae

1W93 の概要

• エントリーDOI: 10.2210/pdb1w93/pdb
• 関連するPDBエントリー: 1OD2 1OD4 1UYR 1UYS 1UYT 1UYV 1W2X
• 分子名称: ACETYL-COENZYME A CARBOXYLASE (2 entities in total)
• 機能のキーワード: obesity, diabetes, fatty acid metabolism, structure-based drug design, allosteric inhibition, polyketide, ligase
• 由来する生物種: SACCHAROMYCES CEREVISIAE (BAKER'S YEAST)
• 細胞内の位置: Cytoplasm: Q00955
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 61523.17

構造登録者

Shen, Y.,Volrath, S.L.,Weatherly, S.C.,Elich, T.D.,Tong, L. (登録日: 2004-10-05, 公開日: 2005-01-04, 最終更新日: 2024-05-08)

主引用文献

Shen, Y.,Volrath, S.L.,Weatherly, S.C.,Elich, T.D.,Tong, L.
A Mechanism for the Potent Inhibition of Eukaryotic Acetyl-Coenzyme a Carboxylase by Soraphen A, a Macrocyclic Polyketide Natural Product
Mol.Cell, 16:881-, 2004

PubMed Abstract: Acetyl-coenzyme A carboxylases (ACCs) have crucial roles in fatty acid metabolism. Soraphen A, a macrocyclic polyketide natural product, is a nanomolar inhibitor against the biotin carboxylase (BC) domain of human, yeast, and other eukaryotic ACCs. Here we report the crystal structures of the yeast BC domain, alone and in complex with soraphen A. Soraphen has extensive interactions with an allosteric site, about 25 A from the active site. The specificity of soraphen is explained by large structural differences between the eukaryotic and prokaryotic BC in its binding site, confirmed by our studies on the effects of single-site mutations in this binding site. Unexpectedly, our structures suggest that soraphen may bind in the BC dimer interface and inhibit the BC activity by disrupting the oligomerization of this domain. Observations from native gel electrophoresis confirm this structural insight. The structural information provides a foundation for structure-based design of new inhibitors against these enzymes.

PubMed: 15610732
DOI: 10.1016/J.MOLCEL.2004.11.034

実験手法

X-RAY DIFFRACTION (2.5 Å)