3H0S

Crystal structure of the carboxyltransferase domain of acetyl-coenzyme A carboxylase in complex with compound 7

3H0S の概要

• エントリーDOI: 10.2210/pdb3h0s/pdb
• 関連するPDBエントリー: 3H0J 3H0Q
• 分子名称: Acetyl-CoA carboxylase, SULFATE ION, 1'-(1H-indazol-7-ylcarbonyl)-6-methylspiro[chromene-2,4'-piperidin]-4(3H)-one, ... (4 entities in total)
• 機能のキーワード: transferase, acetyl-coa carboxylase, carboxyltransferase, inhibitor, acc, ct, atp-binding, biotin, cytoplasm, fatty acid biosynthesis, ligase, lipid synthesis, metal-binding, multifunctional enzyme, nucleotide-binding
• 由来する生物種: Saccharomyces cerevisiae (yeast)
• 細胞内の位置: Cytoplasm: Q00955
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 263128.38

構造登録者

Vajdos, F. (登録日: 2009-04-10, 公開日: 2010-04-07, 最終更新日: 2023-09-06)

主引用文献

Corbett, J.W.,Freeman-Cook, K.D.,Elliott, R.,Vajdos, F.,Rajamohan, F.,Kohls, D.,Marr, E.,Zhang, H.,Tong, L.,Tu, M.,Murdande, S.,Doran, S.D.,Houser, J.A.,Song, W.,Jones, C.J.,Coffey, S.B.,Buzon, L.,Minich, M.L.,Dirico, K.J.,Tapley, S.,McPherson, R.K.,Sugarman, E.,Harwood, H.J.,Esler, W.
Discovery of small molecule isozyme non-specific inhibitors of mammalian acetyl-CoA carboxylase 1 and 2.
Bioorg.Med.Chem.Lett., 20:2383-2388, 2010

PubMed Abstract: Screening Pfizer's compound library resulted in the identification of weak acetyl-CoA carboxylase inhibitors, from which were obtained rACC1 CT-domain co-crystal structures. Utilizing HTS hits and structure-based drug discovery, a more rigid inhibitor was designed and led to the discovery of sub-micromolar, spirochromanone non-specific ACC inhibitors. Low nanomolar, non-specific ACC-isozyme inhibitors that exhibited good rat pharmacokinetics were obtained from this chemotype.

PubMed: 20219367
DOI: 10.1016/j.bmcl.2009.04.091

実験手法

X-RAY DIFFRACTION (2.43 Å)