9OTP

Human glutamine synthetase R298A decamer under turnover conditions

9OTP の概要

• エントリーDOI: 10.2210/pdb9otp/pdb
• EMDBエントリー: 70844
• 分子名称: Glutamine synthetase, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: glutamine synthetase, glutamate-ammonia ligase, type ii, ligase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 425080.96

構造登録者

Greene, E.R.,Muniz, R.S.,Kollman, J.M.,Fraser, J.S. (登録日: 2025-05-27, 公開日: 2025-07-02, 最終更新日: 2025-07-23)

主引用文献

Greene, E.,Muniz, R.,Yamamura, H.,Hoff, S.E.,Bajaj, P.,Lee, D.J.,Thompson, E.M.,Arada, A.,Lee, G.M.,Bonomi, M.,Kollman, J.M.,Fraser, J.S.
Product-stabilized filamentation by human glutamine synthetase allosterically tunes metabolic activity.
Biorxiv, 2025

PubMed Abstract: To maintain metabolic homeostasis, enzymes must adapt to fluctuating nutrient levels through mechanisms beyond gene expression. Here, we demonstrate that human glutamine synthetase (GS) can reversibly polymerize into filaments aided by a composite binding site formed at the filament interface by the product, glutamine. Time-resolved cryo-electron microscopy (cryo-EM) confirms that glutamine binding stabilizes these filaments, which in turn exhibit reduced catalytic specificity for ammonia at physiological concentrations. This inhibition appears induced by a conformational change that remodulates the active site loop ensemble gating substrate entry. Metadynamics ensemble refinement revealed >10 Å conformational range for the active site loop and that the loop is stabilized by transient contacts. This disorder is significant, as we show that the transient contacts which stabilize this loop in a closed conformation are essential for catalysis both and in cells. We propose that GS filament formation constitutes a negative-feedback mechanism, directly linking product concentration to the structural and functional remodeling of the enzyme.

PubMed: 40631248
DOI: 10.1101/2025.07.04.663231

実験手法

ELECTRON MICROSCOPY (1.95 Å)