3TDC

Crystal Structure of Human Acetyl-CoA carboxylase 2

3TDC の概要

• エントリーDOI: 10.2210/pdb3tdc/pdb
• 分子名称: Acetyl-CoA carboxylase 2 variant, 1-[3-({4-[(5S)-3,3-dimethyl-1-oxo-2-oxa-7-azaspiro[4.5]dec-7-yl]piperidin-1-yl}carbonyl)-1-benzothiophen-2-yl]-3-ethylurea (3 entities in total)
• 機能のキーワード: biotin, malonyl-coa, carboxylase, ligase-ligase inhibitor complex, ligase/ligase inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 87103.67

構造登録者

Dougan, D.R.,Mol, C.D. (登録日: 2011-08-10, 公開日: 2011-10-12, 最終更新日: 2023-09-13)

主引用文献

Yamashita, T.,Kamata, M.,Endo, S.,Yamamoto, M.,Kakegawa, K.,Watanabe, H.,Miwa, K.,Yamano, T.,Funata, M.,Sakamoto, J.,Tani, A.,Mol, C.D.,Zou, H.,Dougan, D.R.,Sang, B.,Snell, G.,Fukatsu, K.
Design, synthesis, and structure-activity relationships of spirolactones bearing 2-ureidobenzothiophene as acetyl-CoA carboxylases inhibitors.
Bioorg.Med.Chem.Lett., 21:6314-6318, 2011

PubMed Abstract: The co-crystal structure of the human acetyl-coenzyme A 2 (ACC2) carboxyl transferase domain and the reported compound CP-640186 (1b) suggested that two carbonyl groups are essential for potent ACC2 inhibition. By focusing on enhancing the interactions between the two carbonyl groups and the amino acid residues Gly(2162) and Glu(2230), we used ligand- and structure-based drug design to discover spirolactones bearing a 2-ureidobenzothiophene moiety.

PubMed: 21944854
DOI: 10.1016/j.bmcl.2011.08.117

実験手法

X-RAY DIFFRACTION (2.41 Å)