4EKE

Crystal structure of GPb in complex with DK11

4EKE の概要

• エントリーDOI: 10.2210/pdb4eke/pdb
• 関連するPDBエントリー: 4EJ2 4EKY 4EL0 4EL5
• 分子名称: Glycogen phosphorylase, muscle form, 3-(beta-D-glucopyranosyl)-6-pentylfuro[2,3-d]pyrimidin-2(3H)-one (3 entities in total)
• 機能のキーワード: alpha/beta protein, transferase
• 由来する生物種: Oryctolagus cuniculus (European rabbit,Japanese white rabbit,domestic rabbit,rabbits)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 95877.41

構造登録者

Kantsadi, A.L.,Skamnaki, V.T.,Leonidas, D.D. (登録日: 2012-04-09, 公開日: 2012-07-25, 最終更新日: 2023-12-06)

主引用文献

Kantsadi, A.L.,Manta, S.,Psarra, A.M.,Dimopoulou, A.,Kiritsis, C.,Parmenopoulou, V.,Skamnaki, V.T.,Zoumpoulakis, P.,Zographos, S.E.,Leonidas, D.D.,Komiotis, D.
The binding of C5-alkynyl and alkylfurano[2,3-d]pyrimidine glucopyranonucleosides to glycogen phosphorylase b: Synthesis, biochemical and biological assessment.
Eur.J.Med.Chem., 54:740-749, 2012

PubMed Abstract: C5-alkynyl and alkylfurano[2,3-d]pyrimidine glucopyranonucleosides have been synthesized and studied as inhibitors of glycogen phosphorylase b (GPb). Kinetic experiments have shown that most of these compounds were low micromolar inhibitors of the enzyme. The best inhibitor was 1-(β-D-glucopyranosyl)-5-ethynyluracil (K(i)=4.7 μM). Crystallographic analysis of these compounds in complex with GPb revealed that inhibitors with a long C5-alkynyl group exploited interactions with β-pocket of the active site and induced significant conformational changes of the 280s loop compared to GPb in complex with compounds with a short C5-alkynyl group. The results highlight the importance in the length of the aliphatic groups used to enhance inhibitory potency for the exploitation of the hydrophobic β-pocket. The best of the inhibitors had also a moderate effect on glycogenolysis in the cellular lever with an IC(50) value of 291.4 μM.

PubMed: 22770609
DOI: 10.1016/j.ejmech.2012.06.029

実験手法

X-RAY DIFFRACTION (2.6 Å)