7Q5I

A glucose-based molecular rotor probes the catalytic site of glycogen phosphorylase.

これはPDB形式変換不可エントリーです。

7Q5I の概要

• エントリーDOI: 10.2210/pdb7q5i/pdb
• 分子名称: Glycogen phosphorylase, muscle form, 2-cyano-3-[4-(dimethylamino)phenyl]-~{N}-[(2~{R},3~{R},4~{S},5~{S},6~{R})-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]propanamide, CARBONATE ION, ... (5 entities in total)
• 機能のキーワード: glycogen phosphorylase, inhibitor, type 2 diabetes, molecular rotors, sugar binding protein
• 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: 98286.07

構造登録者

Neofytos, D.D.,Chrysina, E.D. (登録日: 2021-11-03, 公開日: 2022-03-02, 最終更新日: 2024-01-31)

主引用文献

Minadakis, M.P.,Mavreas, K.F.,Neofytos, D.D.,Paschou, M.,Kogkaki, A.,Athanasiou, V.,Mamais, M.,Veclani, D.,Iatrou, H.,Venturini, A.,Chrysina, E.D.,Papazafiri, P.,Gimisis, T.
A glucose-based molecular rotor inhibitor of glycogen phosphorylase as a probe of cellular enzymatic function.
Org.Biomol.Chem., 20:2407-2423, 2022

PubMed Abstract: Molecular rotors belong to a family of fluorescent compounds characterized as molecular switches, where a fluorescence on/off signal signifies a change in the molecule's microenvironment. Herein, the successful synthesis and detailed study of ()-2-cyano-3-(-(dimethylamino)phenyl)--(β-D-glucopyranosyl)acrylamide (RotA), is reported. RotA was found to be a strong inhibitor of rabbit muscle glycogen phosphorylase (RMGP), that binds at the catalytic site of the enzyme. RotA's interactions with the residues lining the catalytic site of RMGP were determined by X-ray crystallography. Spectroscopic studies coupled with theoretical calculations proved that RotA is a molecular rotor. When bound in the catalytic channel of RMGP, it behaved as a light switch, generating a strong fluorescence signal, allowing utilization of RotA as a probe that locates glycogen phosphorylase (GP). RotA, mono-, di- and per-acetylated derivatives, as well as nanoparticles with RotA encapsulated in polyethylene glycol-poly-L-histidine, were used in live cell fluorescence microscopy imaging to test the delivery of RotA through the plasma membrane of HepG2 and A431 cells, with the nanoparticles providing the best results. Once in the intracellular milieu, RotA exhibits remarkable colocalization with GP and significant biological effects, both in cell growth and inhibition of GP.

PubMed: 35119451
DOI: 10.1039/d1ob02211c

実験手法

X-RAY DIFFRACTION (1.8 Å)