7WX4

GK domain of Drosophila P5CS filament with glutamate and ATPgammaS

7WX4 の概要

• エントリーDOI: 10.2210/pdb7wx4/pdb
• EMDBエントリー: 32876
• 分子名称: Delta-1-pyrroline-5-carboxylate synthase (1 entity in total)
• 機能のキーワード: glutamate-bound, filament, aldh18a1, delta-1-pyrroline-5-carboxylate synthase, biosynthetic protein, transferase
• 由来する生物種: Drosophila melanogaster (fruit fly)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 168396.45

構造登録者

Liu, J.L.,Zhong, J.,Guo, C.J.,Zhou, X. (登録日: 2022-02-14, 公開日: 2022-04-06, 最終更新日: 2024-06-26)

主引用文献

Zhong, J.,Guo, C.J.,Zhou, X.,Chang, C.C.,Yin, B.,Zhang, T.,Hu, H.,Lu, G.M.,Liu, J.L.
Structural basis of dynamic P5CS filaments.
Elife, 11:-, 2022

PubMed Abstract: The bifunctional enzyme Δ-pyrroline-5-carboxylate synthase (P5CS) is vital to the synthesis of proline and ornithine, playing an essential role in human health and agriculture. Pathogenic mutations in the P5CS gene (ALDH18A1) lead to neurocutaneous syndrome and skin relaxation connective tissue disease in humans, and P5CS deficiency seriously damages the ability to resist adversity in plants. We have recently found that P5CS forms cytoophidia in vivo and filaments in vitro. However, it is difficult to appreciate the function of P5CS filamentation without precise structures. Using cryo-electron microscopy, here we solve the structures of full-length P5CS in three states at resolution from 3.1 to 4.3 Å. We observe distinct ligand-binding states and conformational changes for the GK and GPR domains, respectively. Divergent helical filaments are assembled by P5CS tetramers and stabilized by multiple interfaces. Point mutations disturbing those interfaces prevent P5CS filamentation and greatly reduce the enzymatic activity. Our findings reveal that filamentation is crucial for the coordination between the GK and GPR domains, providing a structural basis for the catalytic function of P5CS filaments.

PubMed: 35286254
DOI: 10.7554/eLife.76107

実験手法

ELECTRON MICROSCOPY (3.4 Å)