|A bifunctional sea anemone peptide with Kunitz type protease and potassium channel inhibiting properties|Peigneur, S.; Billen, B.; Derua, R.; Waelkens, E.; Debaveye, S.; Béress, L.; Tytgat, J. (2011). A bifunctional sea anemone peptide with Kunitz type protease and potassium channel inhibiting properties. Biochem. Pharmacol. 82(1): 81-90. https://hdl.handle.net/10.1016/j.bcp.2011.03.023
In: Biochemical Pharmacology. Pergamon Press: London; New York. ISSN 0006-2952; e-ISSN 1873-2968
Anthopleura elegantissima (Brandt, 1835) [WoRMS]
Anthopleura elegantissima; KV channel inhibitor; Sea anemone toxin; Protease inhibitor
|Auteurs|| || Top |
- Peigneur, S.
- Billen, B.
- Derua, R.
- Waelkens, E.
- Debaveye, S.
- Béress, L.
- Tytgat, J.
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 Anthopleura elegantissima, 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 (KVs), which also include the kalicludines from Anemonia sulcata. 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 Xenopus laevis oocytes: 13 cloned voltage-gated potassium channels (KV1.1–KV1.6, KV1.1 triple mutant, KV2.1, KV3.1, KV4.2, KV4.3, hERG, the insect channel Shaker IR), 2 cloned hyperpolarization-activated cyclic nucleotide-sensitive cation non-selective channels (HCN1 and HCN2) and 8 cloned voltage-gated sodium channels (NaV1.2–NaV1.8 and the insect channel DmNaV1). Our data show that APEKTx1 selectively blocks KV1.1 channels in a very potent manner with an IC50 value of 0.9 nM. Furthermore, we compared the trypsin inhibitory activity of this toxin with BPTI. APEKTx1 inhibits trypsin with a dissociation constant of 124 nM. In conclusion, this study demonstrates that APEKTx1 has the unique feature to combine the dual functionality of a potent and selective blocker of KV1.1 channels with that of a competitive inhibitor of trypsin.