Subtilisin Kexin Isozyme-1 (SKI-1): Production, purification, inhibitor design and biochemical applications

  • Dayani Mohottalage
  • Natalie Goto
  • Ajoy Basak
Part of the Advances in Experimental Medicine and Biology book series (volume 611)


Subtilisin Kexin Isozyme-1 (SKI-1) belongs to pyrolysin branch of mammalian subtilases [1, 2]. It is synthesized as a membrane bound inactive precursor protein and undergoes auto-catalytic shedding at KHQKLL935⇓ to produce active 98kDa soluble form [3]. This endoprotease cleaves precursor proteins at the motif (R-X-L/I-L/T/K↓), X = any amino acid except Cys. Presence of an additional P7-Tyr greatly enhances SKI-1 recognition [3]. SKI-1 plays roles in cholesterol/lipid synthesis, cartilage development and hemorrhagic fever infections caused by Lassa, Crimean-Congo and Lymphocytic Choriomeningitis viruses [3]. For this reason attention has been focussed on the production of active soluble form of this enzyme and its inhibitors. We have previously described C-terminal modified and pseudopeptide based inhibitors as well as assay of this enzyme [4]. In this study we produced a soluble recombinant human (h) SKI-1 and designed a new miniserpin inhibitor of SKI-1 using the...


Lymphocytic Choriomeningitis Fever Infection Lassa Virus Enzyme Kinetic Study Tetrapeptide Sequence 
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Funds from NSERC, Canada.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Dayani Mohottalage
    • 1
  • Natalie Goto
    • 2
  • Ajoy Basak
    • 1
  1. 1.Hormones Growth and Development Program, Regional Protein Chemistry CenterOttawa Health Research Institute, U OttawaOttawaCANADA
  2. 2.Chemistry DepartmentU Ottawa, D'Iorio Hall, 10 Marie-CurieOttawaCANADA

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