3TDC

Crystal Structure of Human Acetyl-CoA carboxylase 2

Summary for 3TDC

• Entry DOI: 10.2210/pdb3tdc/pdb
• Descriptor: 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)
• Functional Keywords: biotin, malonyl-coa, carboxylase, ligase-ligase inhibitor complex, ligase/ligase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 87103.67

Authors

Dougan, D.R.,Mol, C.D. (deposition date: 2011-08-10, release date: 2011-10-12, Last modification date: 2023-09-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.41 Å)