Huwentoxin 1 (HwTx1)

HWTX-I is the most abundant toxic component in the venom of S. huwena. It inhibits presynaptic N-type Ca2+ channels. The molecular weight of HWTX-I is 3750 Da. The toxin comprises 33 residues, including six cysteines that form three disulfide linkages. These were assigned as Cys2-Cys17, Cys9-Cys22, and Cys16-Cys29 and are buried within the molecule. The molecule adopts a compact structure consisting of a small triple-stranded antiparallel beta-sheet and five beta-turns. It was found that the structure contains an inhibitor cystine knot (ICK) motif. To form this motif, three disulfide bridges are needed. Two of them create a loop through which the third disulfide bridge passes. The structure of HWTX-I is very stable, secondary structure elements do not significantly alter under different pH conditions or after heating. HWTX-I selectively inhibits N-type HVA channels.[9] A recent study found that HWTX-I also inhibits Na+ channels.