Skip to Main content Skip to Navigation
Journal articles

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

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.
Document type :
Journal articles
Complete list of metadata

Cited literature [39 references]  Display  Hide  Download

https://hal.archives-ouvertes.fr/hal-00701259
Contributor : Hal Peer <>
Submitted on : Friday, May 25, 2012 - 2:53:27 AM
Last modification on : Tuesday, July 23, 2019 - 9:30:03 AM
Long-term archiving on: : Thursday, December 15, 2016 - 9:34:21 AM

File

PEER_stage2_10.1016%2Fj.bcp.20...
Files produced by the author(s)

Identifiers

Collections

Citation

Steve Peigneur, Bert Billen, Rita Derua, Etienne Waelkens, Sarah Debaveye, et al.. A bifunctional sea anemone peptide with Kunitz type protease and potassium channel inhibiting properties.. Biochemical Pharmacology, Elsevier, 2011, 82 (1), pp.81. ⟨10.1016/j.bcp.2011.03.023⟩. ⟨hal-00701259⟩

Share

Metrics

Record views

181

Files downloads

446