Hainantoxins specifically inhibit tetrodotoxin-sensitive Voltage-gated sodium channels, thereby causing blockage of neuromuscular transmission and paralysis.
[1][2][4][5][6][7][8][9][10][11] Hainantoxins I, III, IV and V show high homology, including the presence of three disulfide bonds that form an inhibitor cysteine knot (ICK) motif.
The complete amino acid sequence of HNTX-II is NH2-LFECSV SCEIEK EGNKD CKKKK CKGGW KCKFN MCVKV-COOH.
[2] The whole amino acid residue sequence of HNTX-V is NH2-ECLGFG KGCNPS NDQCCK SANLVC SRKHRW CKYEI-COOH.
HNTX-I specifically blocks mammalian Nav1.2 and insect para/tipE channels expressed in Xenopus laevis oocytes.
[1][2] In HNTX-I, the positively charged residues and a vicinal hydrophobic patch have most influence on the binding to the sodium channels.
[4] HNTX-IV has a positively charged patch containing the amino acids Arg26, Lys27, His28, Arg29 and Lys32, of which Lys27, Arg29 and Lys32 are the most important for interaction with the TTX-S VGSCs.
[10][15] HNTX-V also shows an interface of positively charged amino acids that are responsible for the binding with the TTX-S VGSCs, where also Lys27 and Arg29 are the most important.
[8] HNTX-III and HNTX-IV have an antagonistic effect on the toxin BMK-I, a toxic protein in the venom of the scorpion Buthus martensii.