A facultative plasminogen-independent thrombolytic enzyme from Sipunculus nudus
Abstract
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.
Article Details
Authors (32)
Mingqing Tang
Guoxing Ma
Chunyan Xu
Hui Yang
Hongjun Lin
Chao Bian
Chengjia Hu
Meiling Lu
Lei Chen
Wencai Jie
Zhen Yue
Jianbo Jian
Yuqing Sun
Key Laboratory of Biomedical Polymers-Ministry of Education, College of Chemistry and Molecular Sciences
Hui Yan
Jingjing Zhou
Xianying Zhang
Shengye Liao
Zhaofa Li
School of Chemistry, South China Normal University 1 , Guangzhou 510006,
Shuangfeng Cai
Yaqing Wu
Kexin Yang
School of Life Science and Technology, ShanghaiTech University
Yanan Xiong
Yonggang Zhao
Zhimin Lv
Xiaoming Xu
State Key Laboratory of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter and College of Chemistry
Chuang Liu
College of Chemistry and Molecular Sciences, Hubei Key Laboratory of Electrochemical Power Sources
Pengliang Xin
Lichao Ye
Xiuling Cui
Qiong Shi
State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences, TaiKang Center for Life and Medical Sciences, College of Life Sciences, Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan University
Xi Chen
Ruian Xu