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The Kunitz-type protein ShPI-1 inhibits serine proteases and voltage-gated potassium channels
García-Fernández, R.; Peigneur, S.; Pons, T.; Alvarez, C.; González, L.; Chávez, M.A.; Tytgat, J. (2016). The Kunitz-type protein ShPI-1 inhibits serine proteases and voltage-gated potassium channels. Toxins 8(4): 110. dx.doi.org/10.3390/toxins8040110
In: Toxins. Multidisciplinary Digital Publishing Institute (MDPI): Basel. ISSN 2072-6651, more
Peer reviewed article  

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Keywords
    Stichodactyla helianthus (Ellis, 1768) [WoRMS]; Marine
Author keywords
    protease inhibitor; Kv channel inhibitor; sea anemone; toxin;Kunitz-type protein

Authors  Top 
  • García-Fernández, R.
  • Peigneur, S., more
  • Pons, T.
  • Alvarez, C.
  • González, L.
  • Chávez, M.A.
  • Tytgat, J., more

Abstract
    The bovine pancreatic trypsin inhibitor (BPTI)-Kunitz-type protein ShPI-1 (UniProt: P31713) is the major protease inhibitor from the sea anemone Stichodactyla helianthus. This molecule is used in biotechnology and has biomedical potential related to its anti-parasitic effect. A pseudo wild-type variant, rShPI-1A, with additional residues at the N- and C-terminal, has a similar three-dimensional structure and comparable trypsin inhibition strength. Further insights into the structure-function relationship of rShPI-1A are required in order to obtain a better understanding of the mechanism of action of this sea anemone peptide. Using enzyme kinetics, we now investigated its activity against other serine proteases. Considering previous reports of bifunctional Kunitz-type proteins from anemones, we also studied the effect of rShPI-1A on voltage-gated potassium (Kv) channels. rShPI-1A binds Kv1.1, Kv1.2, and Kv1.6 channels with IC50 values in the nM range. Hence, ShPI-1 is the first member of the sea anemone type 2 potassium channel toxins family with tight-binding potency against several proteases and different Kv1 channels. In depth sequence analysis and structural comparison of ShPI-1 with similar protease inhibitors and Kv channel toxins showed apparent non-sequence conservation for known key residues. However, we detected two subtle patterns of coordinated amino acid substitutions flanking the conserved cysteine residues at the N- and C-terminal ends.

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