5O54

Glycogen Phosphorylase b in complex with 29a

5O54 の概要

• エントリーDOI: 10.2210/pdb5o54/pdb
• 関連するPDBエントリー: 5O50 5O52
• 分子名称: Glycogen phosphorylase, muscle form, PYRIDOXAL-5'-PHOSPHATE, (2~{R},3~{S},4~{R},5~{R},6~{R})-5-azanyl-2-(hydroxymethyl)-6-(5-phenyl-4~{H}-1,2,4-triazol-3-yl)oxane-3,4-diol, ... (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: 98324.06

構造登録者

Kyriakis, E.,Solovou, T.G.A.,Stravodimos, G.A.,Kantsadi, A.L.,Chatzileontiadou, D.S.,Skamnaki, V.T.,Leonidas, D.D. (登録日: 2017-05-31, 公開日: 2017-09-27, 最終更新日: 2025-04-09)

主引用文献

Bokor, E.,Kyriakis, E.,Solovou, T.G.A.,Koppany, C.,Kantsadi, A.L.,Szabo, K.E.,Szakacs, A.,Stravodimos, G.A.,Docsa, T.,Skamnaki, V.T.,Zographos, S.E.,Gergely, P.,Leonidas, D.D.,Somsak, L.
Nanomolar Inhibitors of Glycogen Phosphorylase Based on beta-d-Glucosaminyl Heterocycles: A Combined Synthetic, Enzyme Kinetic, and Protein Crystallography Study.
J. Med. Chem., 60:9251-9262, 2017

PubMed Abstract: Aryl substituted 1-(β-d-glucosaminyl)-1,2,3-triazoles as well as C-β-d-glucosaminyl 1,2,4-triazoles and imidazoles were synthesized and tested as inhibitors against muscle and liver isoforms of glycogen phosphorylase (GP). While the N-β-d-glucosaminyl 1,2,3-triazoles showed weak or no inhibition, the C-β-d-glucosaminyl derivatives had potent activity, and the best inhibitor was the 2-(β-d-glucosaminyl)-4(5)-(2-naphthyl)-imidazole with a K value of 143 nM against human liver GPa. An X-ray crystallography study of the rabbit muscle GPb inhibitor complexes revealed structural features of the strong binding and offered an explanation for the differences in inhibitory potency between glucosyl and glucosaminyl derivatives and also for the differences between imidazole and 1,2,4-triazole analogues.

PubMed: 28925695
DOI: 10.1021/acs.jmedchem.7b01056

実験手法

X-RAY DIFFRACTION (2.45 Å)