期刊
TOXINS
卷 8, 期 4, 页码 -出版社
MDPI AG
DOI: 10.3390/toxins8040110
关键词
protease inhibitor; Kv channel inhibitor; sea anemone; toxin; Kunitz-type protein
资金
- Fonds Wetenschappleijk Onderzoek Vlaanderen [G.0433.12, GOE3414N]
- Inter-University Attraction Poles Program, Belgian State, Belgian Science Policy [IUAP 7/10]
- Katholieke Universiteit Leuven [OT/12/081]
- TEAM/Own Initiatives-Programme [ZEIN2013Z134]
- CYTED-BIOTOX [212RT0467]
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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