Product-stabilized filamentation by human glutamine synthetase allosterically tunes metabolic activity.

Human glutamine synthetase forms product-stabilized filaments that reduce catalytic specificity at physiological glutamine levels.

• Why it matters: Understanding enzyme regulation beyond gene expression is crucial for insights into metabolic homeostasis, especially how enzymes adapt to nutrient fluctuations.
• What they did: The study used cryo-EM and metadynamics ensemble refinement to show that glutamine binding stabilizes filaments and alters the enzyme’s active site, affecting substrate gating and catalysis.
• The result: Filament formation acts as a negative-feedback mechanism, linking product concentration to enzyme structure and function, which may regulate metabolic activity in cells.