9OTQ
Human glutamine synthetase filament apo
Summary for 9OTQ
| Entry DOI | 10.2210/pdb9otq/pdb |
| EMDB information | 70845 |
| Descriptor | Glutamine synthetase, MAGNESIUM ION (2 entities in total) |
| Functional Keywords | glutamine synthetase, glutamate-ammonia ligase, filament, type ii, ligase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 20 |
| Total formula weight | 842854.14 |
| Authors | Greene, E.R.,Muniz, R.S.,Kollman, J.M.,Fraser, J.S. (deposition date: 2025-05-27, release date: 2025-07-02, Last modification date: 2025-07-23) |
| Primary citation | 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 Cited by 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: 40631248DOI: 10.1101/2025.07.04.663231 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.27 Å) |
Structure validation
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