5OX3

Glycogen Phosphorylase in complex with SzB102v

5OX3 の概要

• エントリーDOI: 10.2210/pdb5ox3/pdb
• 関連するPDBエントリー: 5OWY 5OWZ 5OX0 5OX1
• 分子名称: Glycogen phosphorylase, muscle form, (1S)-1,5-anhydro-1-[3-(4-hydroxyphenyl)-1H-1,2,4-triazol-5-yl]-D-glucitol, PYRIDOXAL-5'-PHOSPHATE, ... (5 entities in total)
• 機能のキーワード: transferase
• 由来する生物種: Oryctolagus cuniculus (Rabbit)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 98341.05

構造登録者

Kyriakis, E.,Stravodimos, G.A.,Kantsadi, A.L.,Chatzileontiadou, D.S.M.,Leonidas, D.D. (登録日: 2017-09-05, 公開日: 2018-02-28, 最終更新日: 2025-04-09)

主引用文献

Kyriakis, E.,Solovou, T.G.A.,Kun, S.,Czifrak, K.,Szocs, B.,Juhasz, L.,Bokor, E.,Stravodimos, G.A.,Kantsadi, A.L.,Chatzileontiadou, D.S.M.,Skamnaki, V.T.,Somsak, L.,Leonidas, D.D.
Probing the beta-pocket of the active site of human liver glycogen phosphorylase with 3-(C-beta-d-glucopyranosyl)-5-(4-substituted-phenyl)-1, 2, 4-triazole inhibitors.
Bioorg. Chem., 77:485-493, 2018

PubMed Abstract: Human liver glycogen phosphorylase (hlGP), a key enzyme in glycogen metabolism, is a valid pharmaceutical target for the development of new anti-hyperglycaemic agents for type 2 diabetes. Inhibitor discovery studies have focused on the active site and in particular on glucopyranose based compounds with a β-1 substituent long enough to exploit interactions with a cavity adjacent to the active site, termed the β-pocket. Recently, C-β-d-glucopyranosyl imidazoles and 1, 2, 4-triazoles proved to be the best known glucose derived inhibitors of hlGP. Here we probe the β-pocket by studying the inhibitory effect of six different groups at the para position of 3-(β-d-glucopyranosyl phenyl)-5-phenyl-, 1, 2, 4-triazoles in hlGP by kinetics and X-ray crystallography. The most bioactive compound was the one with an amine substituent to show a K value of 0.43 μM. Structural studies have revealed the physicochemical diversity of the β-pocket providing information for future rational inhibitor design studies.

PubMed: 29454281
DOI: 10.1016/j.bioorg.2018.02.008

実験手法

X-RAY DIFFRACTION (1.9 Å)