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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)

Introduction

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...

Keywords

Lymphocytic Choriomeningitis Fever Infection Lassa Virus Enzyme Kinetic Study Tetrapeptide Sequence 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Funds from NSERC, Canada.

References

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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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