3KC1

Crystal structure of human liver FBPase in complex with tricyclic inhibitor 19a

3KC1 の概要

• エントリーDOI: 10.2210/pdb3kc1/pdb
• 関連するPDBエントリー: 3KBZ 3KC0
• 分子名称: Fructose-1,6-bisphosphatase 1, {[(7-carbamoyl-8H-indeno[1,2-d][1,3]thiazol-4-yl)oxy]methyl}phosphonic acid (3 entities in total)
• 機能のキーワード: hydrolase, allosteric enzyme, carbohydrate metabolism, disease mutation, gluconeogenesis, magnesium, metal-binding, polymorphism
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 148217.97

構造登録者

Takahashi, M.,Sone, J.,Hanzawa, H. (登録日: 2009-10-20, 公開日: 2010-02-02, 最終更新日: 2023-11-01)

主引用文献

Tsukada, T.,Takahashi, M.,Takemoto, T.,Kanno, O.,Yamane, T.,Kawamura, S.,Nishi, T.
Structure-based drug design of tricyclic 8H-indeno[1,2-d][1,3]thiazoles as potent FBPase inhibitors.
Bioorg.Med.Chem.Lett., 20:1004-1007, 2010

PubMed Abstract: With the goal of improving metabolic stability and further enhancing FBPase inhibitory activity, a series of tricyclic 8H-indeno[1,2-d][1,3]thiazoles was designed and synthesized with the aid of structure-based drug design. Extensive SAR studies led to the discovery of 19a with an IC(50) value of 1nM against human FBPase. X-ray crystallographic studies revealed that high affinity of 19a was due to the hydrophobic interaction arising from better shape complementarity and to the hydrogen bonding network involving the side chain on the tricyclic scaffold.

PubMed: 20045638
DOI: 10.1016/j.bmcl.2009.12.056

実験手法

X-RAY DIFFRACTION (2.25 Å)