8ZVX

Crystal structure of snFPITE-n2

8ZVX の概要

• エントリーDOI: 10.2210/pdb8zvx/pdb
• 分子名称: snFPITE-n2 A chain, snFPITE-n2 B chain, phenylmethanesulfonic acid, ... (7 entities in total)
• 機能のキーワード: fibrin lysis, fibrinogen lysis, plasminogen activation, proteinase, blood clotting
• 由来する生物種: Sipunculus nudus; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 51374.74

構造登録者

Chen, X.,Yang, H. (登録日: 2024-06-12, 公開日: 2025-04-02, 最終更新日: 2025-05-07)

主引用文献

Tang, M.,Ma, G.,Xu, C.,Yang, H.,Lin, H.,Bian, C.,Hu, C.,Lu, M.,Chen, L.,Jie, W.,Yue, Z.,Jian, J.,Sun, Y.,Yan, H.,Zhou, J.,Zhang, X.,Liao, S.,Li, Z.,Cai, S.,Wu, Y.,Yang, K.,Xiong, Y.,Zhao, Y.,Lv, Z.,Xu, X.,Liu, C.,Xin, P.,Ye, L.,Cui, X.,Shi, Q.,Chen, X.,Xu, R.
A facultative plasminogen-independent thrombolytic enzyme from Sipunculus nudus.
Nat Commun, 16:3852-3852, 2025

PubMed Abstract: Current thrombolytic therapies primarily function by converting plasminogen into plasmin, a process dependent on the fibrin-activator complex. This dependence, coupled with the substantial molecular size of plasmin, constrains its effectiveness in degrading D-dimer and restricts its diffusion within thrombi. Here, we introduce a small facultative plasminogen-independent thrombolytic enzyme, snFPITE, isolated from Sipunculus nudus. Compared to traditional thrombolytic agents, snFPITE does not require plasminogen for thrombolysis, although its presence enhances lytic activity. This enzyme fully degrades cross-linked fibrin without leaving residual nondegradable D-dimer and generates a smaller fibrinolytic-active agent from plasminogen. A series of male rats and mice models further confirm that snFPITE is a safety injectable thrombolytic agent. Mechanistically, snFPITE activates plasminogen and degrades fibrin(ogen) in a multisite cleavage manner. snFPITE is inhibited by plasminogen activator inhibitor 1 and α2-antiplasmin via a competitive inhibition. We further identify 28 snFPITE candidate sequences, of which 10 are confirmed as functional genes.

PubMed: 40274794
DOI: 10.1038/s41467-025-58915-y

実験手法

X-RAY DIFFRACTION (1.5 Å)