The Kunitz-Type Protein ShPI-1 Inhibits Serine Proteases and Voltage-Gated Potassium Channels
| Autor: | María A. Chávez, Rossana García-Fernández, Steve Peigneur, Carlos Alvarez, Tirso Pons, Lidice González, Jan Tytgat |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
sea anemone Health Toxicology and Mutagenesis medicine.medical_treatment lcsh:Medicine TRYPSIN Toxicology Serine Xenopus laevis BINDING Kunitz-type protein PEPTIDE HETERACTIS-CRISPA toxin Stichodactyla helianthus ALPHA-DENDROTOXIN biology ACTIVE-SITE Voltage-gated potassium channel Trypsin Recombinant Proteins Potassium channel Biochemistry Potassium Channels Voltage-Gated Food Science & Technology BLOCKING TOXINS Life Sciences & Biomedicine medicine.drug Proteases Serine Proteinase Inhibitors Molecular Sequence Data Article protease inhibitor Kv channel inhibitor 03 medical and health sciences Aprotinin Potassium Channel Blockers medicine Animals Amino Acid Sequence Science & Technology Protease lcsh:R ANEMONE STICHODACTYLA-HELIANTHUS biology.organism_classification Protease inhibitor (biology) 030104 developmental biology NEUROTOXIN Oocytes Serine Proteases SENSITIVE K+ CHANNELS |
| Zdroj: | Toxins, Vol 8, Iss 4, p 110 (2016) Toxins; Volume 8; Issue 4; Pages: 110 Toxins |
| ISSN: | 2072-6651 |
| Popis: | 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. ispartof: TOXINS vol:8 issue:4 ispartof: location:Switzerland status: published |
| Databáze: | OpenAIRE |
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