6S4H

The crystal structure of glycogen phosphorylase in complex with 8

6S4H の概要

• エントリーDOI: 10.2210/pdb6s4h/pdb
• 分子名称: Glycogen phosphorylase, muscle form, (2~{R},3~{S},4~{R},5~{R},6~{S})-2-(hydroxymethyl)-6-(2-phenyl-1~{H}-imidazol-4-yl)oxane-3,4,5-triol, DIMETHYL SULFOXIDE, ... (5 entities in total)
• 機能のキーワード: phosphorylase, inhibitor, c-beta-d-glucopyranosyl imidazole, 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: 98053.99

構造登録者

Kyriakis, E.,Solovou, T.G.A.,Papaioannou, O.S.E.,Skamnaki, V.T.,Leonidas, D.D. (登録日: 2019-06-28, 公開日: 2020-02-19, 最終更新日: 2025-04-09)

主引用文献

Kyriakis, E.,Karra, A.G.,Papaioannou, O.,Solovou, T.,Skamnaki, V.T.,Liggri, P.G.V.,Zographos, S.E.,Szennyes, E.,Bokor, E.,Kun, S.,Psarra, A.G.,Somsak, L.,Leonidas, D.D.
The architecture of hydrogen and sulfur sigma-hole interactions explain differences in the inhibitory potency of C-beta-d-glucopyranosyl thiazoles, imidazoles and an N-beta-d glucopyranosyl tetrazole for human liver glycogen phosphorylase and offer new insights to structure-based design.
Bioorg.Med.Chem., 28:115196-115196, 2020

PubMed Abstract: C-Glucopyranosyl imidazoles, thiazoles, and an N-glucopyranosyl tetrazole were assessed in vitro and ex vivo for their inhibitory efficiency against isoforms of glycogen phosphorylase (GP; a validated pharmacological target for the development of anti-hyperglycaemic agents). Imidazoles proved to be more potent inhibitors than the corresponding thiazoles or the tetrazole. The most potent derivative has a 2-naphthyl substituent, a K value of 3.2 µM for hepatic glycogen phosphorylase, displaying also 60% inhibition of GP activity in HepG2 cells, compared to control vehicle treated cells, at 100 μM. X-Ray crystallography studies of the protein - inhibitor complexes revealed the importance of the architecture of inhibitor associated hydrogen bonds or sulfur σ-hole bond interactions to Asn284 OD1, offering new insights to structure-based design efforts. Moreover, while the 2-glucopyranosyl-tetrazole seems to bind differently from the corresponding 1,2,3-triazole compound, the two inhibitors are equipotent.

PubMed: 31767404
DOI: 10.1016/j.bmc.2019.115196

実験手法

X-RAY DIFFRACTION (2.45 Å)