title: Joannsin, a novel Kunitz-type FXa inhibitor from the venom of Prospirobolus joannsi.
abstract: The repugnatorial glands of millipedes release various defensive chemical secretions. Although varieties of such defensive secretions have been studied, none of them is protein or peptide. Herein, a novel factor Xa (FXa) inhibitor named joannsin was identified and characterised from repugnatorial glands of Prospirobolus joannsi. Joannsin is composed of 72 amino acid residues including six cysteines, which form three intra-molecular disulfide bridges. It is a member of Kunitz-type protease inhibitor family, members of which are also found in the secretory glands of other arthropods. Recombinant joannsin exhibited remarkable inhibitory activity against trypsin and FXa with a Ki of 182.7 ± 14.6 and 29.5 ± 4.7 nM, respectively. Joannsin showed strong anti-thrombosis functions in vitro and in vivo. Joannsin is the first peptide component in millipede repugnatorial glands to be identified and is a potential candidate and/or template for the development of anti-thrombotic agents. These results also indicated that there is Kunitz-type protease inhibitor toxin in millipede repugnatorial glands as in other arthropods secretory glands.
authors.forename: Ning
authors.initials: N
authors.lastname: Luan
authors.forename: Chunling
authors.initials: C
authors.lastname: Zhou
authors.forename: Pengpeng
authors.initials: P
authors.lastname: Li
authors.forename: Rose
authors.initials: R
authors.lastname: Ombati
authors.forename: Xiuwen
authors.initials: X
authors.lastname: Yan
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Mo
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Rong
authors.affiliation: Ren Lai, Zilei Duan, or Ruiqiang Zheng, Key Laboratory of Microbiological Engineering of Agricultural Environment, Ministry of Agriculture, College of Life Sciences, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China, Tel./Fax: +86 25 843968, E-mail: rlai72@njau.edu.cn (R. L.), duanzileikiz@126.com (Z. D.) or 13952721411@163.com (R. Z.).
authors.forename: Ren
authors.initials: R
authors.lastname: Lai
authors.forename: Zilei
authors.initials: Z
authors.lastname: Duan
authors.forename: Ruiqiang
authors.initials: R
authors.lastname: Zheng
mesh_terms: D000818:Animals; D060829:Arthropod Proteins / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D001180:Arthropod Venoms / Q000378:metabolism*; D001181:Arthropods / Q000502:physiology*; D001777:Blood Coagulation; D002351:Carrageenan; D003001:Cloning, Molecular; D015951:Factor Xa / Q000378:metabolism*; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D011720:Pyrazoles / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D012543:Scent Glands / Q000378:metabolism*; D013927:Thrombosis / Q000139:chemically induced / Q000188:drug therapy*; D014357:Trypsin / Q000378:metabolism
chemical_list: D060829:Arthropod Proteins; D001180:Arthropod Venoms; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D011720:Pyrazoles; D011728:Pyridones; D011994:Recombinant Proteins; C522181:apixaban; D002351:Carrageenan; D014357:Trypsin; D015951:Factor Xa
keywords: Kunitz-type inhibitor; Millipede; factor Xa; repugnatorial gland; thrombosis