3H1V

Human glucokinase in complex with a synthetic activator

3H1V の概要

• エントリーDOI: 10.2210/pdb3h1v/pdb
• 分子名称: Glucokinase, alpha-D-glucopyranose, 1-({5-[4-(methylsulfonyl)phenoxy]-2-pyridin-2-yl-1H-benzimidazol-6-yl}methyl)pyrrolidine-2,5-dione, ... (5 entities in total)
• 機能のキーワード: glucokinase, diabetes, allosteric activator, alternative splicing, atp-binding, diabetes mellitus, disease mutation, glycolysis, kinase, nucleotide-binding, polymorphism, transferase
• 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: 51290.15

構造登録者

Kamata, K.,Takahashi, K. (登録日: 2009-04-14, 公開日: 2009-10-06, 最終更新日: 2024-03-20)

主引用文献

Takahashi, K.,Hashimoto, N.,Nakama, C.,Kamata, K.,Sasaki, K.,Yoshimoto, R.,Ohyama, S.,Hosaka, H.,Maruki, H.,Nagata, Y.,Eiki, J.,Nishimura, T.
The design and optimization of a series of 2-(pyridin-2-yl)-1H-benzimidazole compounds as allosteric glucokinase activators.
Bioorg.Med.Chem., 17:7042-7051, 2009

PubMed Abstract: The optimization of a series of benzimidazole glucokinase activators is described. We identified a novel and potent achiral benzimidazole derivative as an allosteric GK activator. This activator was designed and synthesized via removal of the chiral center of the lead compound, 6-(N-acylpyrrolidin-2-yl)benzimidazole. The activator exhibited good PK profiles in rats and dogs, and significant hypoglycemic efficacy at 1 mg/kg po dosing in a rat OGTT model. The binding site and binding mode of the benzimidazole class of GKA with GK protein was confirmed by X-ray crystallographic analysis.

PubMed: 19736020
DOI: 10.1016/j.bmc.2009.05.037

実験手法

X-RAY DIFFRACTION (2.11 Å)