The Kunitz-Type Protein ShPI-1 Inhibits Serine Proteases and Voltage-Gated Potassium Channels
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 vari...
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| Format: | Article |
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MDPI AG
2016-04-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/8/4/110 |
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| author | Rossana García-Fernández Steve Peigneur Tirso Pons Carlos Alvarez Lidice González María A. Chávez Jan Tytgat |
| author_facet | Rossana García-Fernández Steve Peigneur Tirso Pons Carlos Alvarez Lidice González María A. Chávez Jan Tytgat |
| author_sort | Rossana García-Fernández |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T08:22:46Z |
| format | Article |
| id | doaj.art-c40928c6dd5d4627bde4a2c17edf194c |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-12-10T08:22:46Z |
| publishDate | 2016-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-c40928c6dd5d4627bde4a2c17edf194c2022-12-22T01:56:19ZengMDPI AGToxins2072-66512016-04-018411010.3390/toxins8040110toxins8040110The Kunitz-Type Protein ShPI-1 Inhibits Serine Proteases and Voltage-Gated Potassium ChannelsRossana García-Fernández0Steve Peigneur1Tirso Pons2Carlos Alvarez3Lidice González4María A. Chávez5Jan Tytgat6Centro de Estudio de Proteínas, Facultad de Biología, Universidad de la Habana, Calle 25 No. 455, 10400 La Habana, CubaLaboratory of Toxicology and Pharmacology, KU Leuven, Campus Gasthuisberg O&N2, Herestraat 49, P.O. Box 922, B-3000 Leuven, BelgiumStructural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), C/Melchor Fernández Almagro 3, Madrid E-28029, SpainCentro de Estudio de Proteínas, Facultad de Biología, Universidad de la Habana, Calle 25 No. 455, 10400 La Habana, CubaCentro de Estudio de Proteínas, Facultad de Biología, Universidad de la Habana, Calle 25 No. 455, 10400 La Habana, CubaCentro de Estudio de Proteínas, Facultad de Biología, Universidad de la Habana, Calle 25 No. 455, 10400 La Habana, CubaLaboratory of Toxicology and Pharmacology, KU Leuven, Campus Gasthuisberg O&N2, Herestraat 49, P.O. Box 922, B-3000 Leuven, BelgiumThe 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.http://www.mdpi.com/2072-6651/8/4/110protease inhibitorKv channel inhibitorsea anemonetoxinKunitz-type protein |
| spellingShingle | Rossana García-Fernández Steve Peigneur Tirso Pons Carlos Alvarez Lidice González María A. Chávez Jan Tytgat The Kunitz-Type Protein ShPI-1 Inhibits Serine Proteases and Voltage-Gated Potassium Channels Toxins protease inhibitor Kv channel inhibitor sea anemone toxin Kunitz-type protein |
| title | The Kunitz-Type Protein ShPI-1 Inhibits Serine Proteases and Voltage-Gated Potassium Channels |
| title_full | The Kunitz-Type Protein ShPI-1 Inhibits Serine Proteases and Voltage-Gated Potassium Channels |
| title_fullStr | The Kunitz-Type Protein ShPI-1 Inhibits Serine Proteases and Voltage-Gated Potassium Channels |
| title_full_unstemmed | The Kunitz-Type Protein ShPI-1 Inhibits Serine Proteases and Voltage-Gated Potassium Channels |
| title_short | The Kunitz-Type Protein ShPI-1 Inhibits Serine Proteases and Voltage-Gated Potassium Channels |
| title_sort | kunitz type protein shpi 1 inhibits serine proteases and voltage gated potassium channels |
| topic | protease inhibitor Kv channel inhibitor sea anemone toxin Kunitz-type protein |
| url | http://www.mdpi.com/2072-6651/8/4/110 |
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