T-type Ca2+-Channel Blocker with Na+/K+-Channel Blocking Activity
ProTx-I was isolated from the venom of the tarantula Thrixopelma pruriens and its primary structure was determined to consist of 35 amino acid residues with three intrachain disulfide bonds[Biochemistry 41, 14734 (2002)]. This peptide shows sequence similarity to hanatoxin1 and belongs to a member of the “inhibitor cystine knot” peptide family.
Glu-Cys-Arg-Tyr-Trp-Leu-Gly-Gly-Cys-Ser- Ala-Gly-Gln-Thr-Cys-Cys-Lys-His-Leu-Val- Cys-Ser-Arg-Arg-His-Gly-Trp-Cys-Val-Trp- Asp-Gly-Thr-Phe-Ser
Like other venomous toxins, ProTx-I exerts inhibitory activities for each ion channels; i) T-type Ca2+ channel [Cav3.1 (α1G), IC50 = 53 nM], ii) Na+ channel [Nav1.2, Nav1.5, Nav1.7 (IC50 = 51 nM), and Nav1.8 (IC50 = 27 nM)], and iii) K+ channel [Kv2.1 (IC50 = 411 nM) and Kv1.3 (40% blocking at 730 nM)].
ProTx-I thus elicits multiple channel blocking activities with certain selectivity since K+ channel inhibitory activity is relatively weak. ProTx-I is one of the first high-affinity ligands to be identified that possess tetrodotoxin-resistant Na+ and T-type Ca2+ channel blocking activity. This peptide should prove useful for elucidating the gating mechanism of voltage-dependent ion channels.
|4409-s||ProTx-I||T-type Ca2+/Na+/K+ Channel Blocker||0.1 mg vial||¥22,000|
|4375-s||Kurtoxin||T-type Ca2+ Channel Blocker||0.1 mg vial||¥30,000|
|4217-v||μ-Conotoxin GIIIB||Na+ Channel Blocker||0.5 mg vial||¥38,000|
|4263-v||μ-Conotoxin GS||Na+ Channel Blocker||0.5 mg vial||¥40,000|