title: A new Kunitz-type plasmin inhibitor from scorpion venom.
abstract: Kunitz-type peptides from venomous animals are an important source of lead drug candidates towards human plasmin, a target of protease-associated diseases. However, no Kunitz-type plasmin inhibitor from venomous scorpion has been characterized. Here, we first investigated plasmin inhibiting activities of eight known Kunitz-type scorpion toxins Hg1, BmKTT-1, BmKTT-2, BmKTT-3, LmKTT-1a, LmKTT-1b, LmKTT-1c and BmKPI, and found a new plasmin inhibitor BmKTT-2, a Kunitz-type toxin peptide from the scorpion Buthus martensi karch. Protease inhibitory activity assay showed that BmKTT-2 potently inhibited plasmin with a Ki value of 8.75 ± 2.05 nM. Structure-function relationship studies between BmKTT-2 and plasmin showed that BmKTT-2 is a classical Kunitz-type plasmin inhibitor: Lys13 in BmKTT-2 is the P1 site, and Ala14 in BmKTT-2 is the P1' site. Interestingly, BmKTT-2 has potent inhibiting activities towards three important digestive serine proteases trypsin, chymotrypsin and elastase, suggesting a good stability for administering oral medications. To the best of our knowledge, BmKTT-2 is the first Kunitz-type human plasmin inhibitor from scorpion venom, providing novel insights into drug developments targeting human plasmin protease.
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Hubei University of Medicine, Hubei, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Hubei University of Medicine, Hubei, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Hubei University of Medicine, Hubei, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Hubei University of Medicine, Hubei, China.
authors.forename: Mingkui
authors.initials: M
authors.lastname: San
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Hubei University of Medicine, Hubei, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Parasitology, College of Basic Medicine, Hubei University of Medicine, Shiyan 442000, Hubei, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Hubei University of Medicine, Hubei, China; Department of Integrated Medicine, General Hospital of Dongfeng, Hubei University of Medicine, Hubei 442000, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei, China.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei, China. Electronic address: ylwu@whu.edu.cn.
authors.forename: Yingliang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Hubei University of Medicine, Hubei, China; State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei, China. Electronic address: chenzy2005@126.com.
authors.forename: Zongyun
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000933:Antifibrinolytic Agents / Q000737:chemistry* / Q000302:isolation & purification; D002942:Circular Dichroism; D004926:Escherichia coli / Q000235:genetics; D005341:Fibrinolysin / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D016297:Mutagenesis, Site-Directed; D012604:Scorpion Venoms / Q000737:chemistry*; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein
chemical_list: D000933:Antifibrinolytic Agents; D012604:Scorpion Venoms; D005341:Fibrinolysin
keywords: BmKTT-2; Kunitz-type; Peptide inhibitor; Plasmin; Scorpion venom