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-Structure paper
| タイトル | Structural and mechanistic diversity of glycogen phosphorylases from gut bacteria. |
|---|---|
| ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 123, Issue 7, Page e2518513123, Year 2026 |
| 掲載日 | 2026年2月17日 |
著者 | Keigo Shobu / Mayu Takai / Hiroki Tanino / Yohta Fukuda / Tsuyoshi Inoue / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Proc Natl Acad Sci U S A / PubMed:41662519 / PubMed Central |
| 手法 | EM (単粒子) / X線回折 |
| 解像度 | 2.63 - 4.03 Å |
| 構造データ | EMDB-62853, PDB-9l6i: EMDB-63736, PDB-9m9p: EMDB-63749, PDB-9ma8: EMDB-63814, PDB-9u3a: EMDB-63816, PDB-9u3k: EMDB-64377, PDB-9uoe: EMDB-64393, PDB-9upe: EMDB-64491, PDB-9utg: EMDB-64514, PDB-9uup: EMDB-64926, PDB-9vbl: EMDB-64927, PDB-9vbm: ![]() EMDB-64931: Cryo-EM map of glycogen phosphorylase from Dorea longicatena (monomer form with extra density) EMDB-65039, PDB-9vfv: ![]() EMDB-65042: Glycogen phosphorylase dimer from E. coli in complex with glycogen EMDB-67417, PDB-20yr: EMDB-67418, PDB-20ys: ![]() PDB-9maq: ![]() PDB-9ukq: ![]() PDB-9ukr: ![]() PDB-9v16: ![]() PDB-9v17: |
| 化合物 | ![]() ChemComp-G1P: ![]() ChemComp-PO4: ![]() ChemComp-AMP: ![]() ChemComp-HOH: |
| 由来 |
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キーワード | TRANSFERASE / glycogen phosphorylase / STRUCTURAL PROTEIN / glycogen metabolism / cryo-EM / gut bacteria |
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segatella copri (バクテリア)
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