A bifunctional sea anemone peptide with Kunitz type protease and potassium channel inhibiting properties.Reportar como inadecuado




A bifunctional sea anemone peptide with Kunitz type protease and potassium channel inhibiting properties. - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

* Corresponding author 1 KU Leuven - Katholieke Universiteit Leuven 2 University of leuven

Abstract : Sea anemone venom is a known source of interesting bioactive compounds, including peptide toxins which are invaluable tools for studying structure and function of voltage-gated potassium channels. APEKTx1 is a novel peptide isolated from the sea anemone , containing 63 amino acids cross-linked by 3 disulfide bridges. Sequence alignment reveals that APEKTx1 is a new member of the type 2 sea anemone peptides targeting voltage-gated potassium channels K-s, which also include the kalicludines from . Similar to the kalicludines, APEKTx1 shares structural homology with both the basic pancreatic trypsin inhibitor BPTI, a very potent Kunitz-type protease inhibitor, and dendrotoxins which are powerful blockers of voltage-gated potassium channels. In this study, APEKTx1 has been subjected to a screening on a wide range of 23 ion channels expressed in oocytes: 13 cloned voltage-gated potassium channels K1.1-K1.6, K1.1 triple mutant, K2.1, K3.1, K4.2, K4.3, hERG, the insect channel IR, 2 cloned hyperpolarization-activated cyclic nucleotide-sensitive cation non-selective channels HCN1 and HCN2 and 8 cloned voltage-gated sodium channels Na1.2-Na1.8 and the insect channel DmNa1. Our data shows that APEKTx1 selectively blocks K1.1 channels in a very potent manner with an IC value of 0.9nM. Furthermore, we compared the trypsin inhibitory activity of this toxin with BPTI. APEKTx1 inhibits trypsin with a dissociation constant of 124nM. In conclusion, this study demonstrates that APEKTx1 has the unique feature to combine the dual functionality of a potent and selective blocker of K1.1 channels with that of a competitive inhibitor of trypsin.

Keywords : K channel inhibitor sea anemone toxin protease inhibitor





Autor: Steve Peigneur - Bert Billen - Rita Derua - Etienne Waelkens - Sarah Debaveye - László Béress Jan Tytgat -

Fuente: https://hal.archives-ouvertes.fr/



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