20YS

R583A mutant of glycogen phosphorylase from Segatella copri in the presence of AMP

20YS の概要

• エントリーDOI: 10.2210/pdb20ys/pdb
• EMDBエントリー: 67418
• 分子名称: Alpha-glucan family phosphorylase (1 entity in total)
• 機能のキーワード: glycogen phosphorylase, transferase
• 由来する生物種: Segatella copri
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 505071.14

構造登録者

Takai, M.,Fukuda, Y. (登録日: 2025-12-03, 公開日: 2026-02-18, 最終更新日: 2026-04-01)

主引用文献

Shobu, K.,Takai, M.,Tanino, H.,Fukuda, Y.,Inoue, T.
Structural and mechanistic diversity of glycogen phosphorylases from gut bacteria.
Proc.Natl.Acad.Sci.USA, 123:e2518513123-e2518513123, 2026

PubMed Abstract: Glycogen phosphorylase (GP) plays a central role in glycogen metabolism. While the structure and regulation of mammalian GPs have been extensively studied, the corresponding mechanisms in gut bacterial GPs remain poorly understood. Here, we investigate GPs from (GP), (GP), and (GP), which represent three phylogenetic clades of GPs, using enzymatic assays, cryo-electron microscopy (cryo-EM), and X-ray crystallography. We find that GP forms a unique pentamer that undergoes adenosine monophosphate (AMP)-dependent assembly into a dimer-of-pentamer, which inhibits activity by restricting substrate access to the catalytic site. GP exists in equilibrium among monomers, dimers, and tetramers, with AMP promoting tetramer dissociation and enhancing catalytic efficiency. In contrast, GP remains predominantly monomeric and is unresponsive to AMP. These findings uncover structural and regulatory diversity among gut bacterial GPs. Notably, the oligomeric states of GPs modulate substrate accessibility and enzyme activation, suggesting a distinct mode of allosteric regulation beyond the canonical T-to-R transition model. Because bacterial GPs contribute to the generation of glucose, their regulation may influence the composition of gut-derived metabolites that affect host glucose homeostasis and insulin sensitivity. Our study provides mechanistic insight into the structural and functional diversity of gut bacterial GPs and lays a foundation for future exploration of microbiome-mediated metabolic interactions.

PubMed: 41662519
DOI: 10.1073/pnas.2518513123

実験手法

ELECTRON MICROSCOPY (2.96 Å)