BmP02

BmP02 toxin, also known as a-KTx9.1 (UniProt Q9NJP7), is a short-chain toxin of 28 amino acids and reticulated by three disulfide bridges initially isolated from the venom of the Chinese scorpion Buthus martensi Karsch. BmP02 has been reported to act on CNS and cardiac Kv4.2 with an IC50 of 850 nM mainly by slowing inactivation kinetics, accelerating the recovery from inactivation and slowing deactivation. As such, BmP02 can be considered as an activator of Kv4.2. However, it has no impact on current amplitude or voltage-dependence of activation or inactivation. Key toxin residues for the interaction with Kv4.2 are Glu4, Glu5, Asp20 and Asp21. BmP02 is also a potent blocker of the Kv1.3 channel with an IC50 of 32 nM. Kv1.3 block mobilizes a different structural domain of BmP02, with residues His9, Lys11 and Lys13 being critical. BmP02 occludes the Kv1.3 pore and thus inhibits the current amplitude without altering channel voltage-dependence. Of note, BmP02 differs from BmP03, another peptide from the same venom, by a single amino acid residue (Lys16 being replaced by Asn16). BmP03 is thus expected to have the same pharmacological profile than BmP02. Similarly, BmP02 differs from Kbot1 by only two residues Asn14 and Lys16 replaced by His and Val, respectively).