omega-Grammotoxin SIA

omega-Grammotoxin SIA (ω-grammotoxin SIA) is a protein toxin that inhibits P, Q, and N voltage-gated calcium channels (Ca²⁺ channels) in neurons.

Sources

The source of ω-grammotoxin SIA is the venom of a tarantula spider (Grammostola rosea).

Chemistry

Amino acid sequence: Asp-Cys-Val-Arg-Phe-Trp-Gly-Lys-Cys-Ser-Gln-Thr-Ser-Asp-Cys-Cys-Pro-His-Leu-Ala-Cys-Lys-Ser-Lys-Trp-Pro-Arg-Asn-Ile-Cys-Val-Trp-Asp-Gly-Ser-Val^[1]

Molecular formula: C₁₇₇H₂₆₈N₅₂O₅₀S₆^[1]

ω-Grammotoxin SIA can be purified from Grammostola rosea venom by reverse phase high performance liquid chromatography.^[2]

Target

ω-Grammotoxin SIA is a 36 amino acid residue protein toxin from spider venom that inhibits P, Q, and N-type voltage-gated calcium channels in neurons. It binds to the channels with high affinity (if closed). It also binds to potassium channels but with lower affinity than to the calcium channels.^[3] The toxin binding site has high affinity when channels are in closed states and low affinity when channels are activated. (4)

Mode of action

It is believed that ω-grammotoxin SIA inhibits channel function by binding with high affinity to closed, resting states of the channel and that bound toxin makes it more difficult for channels to be opened by depolarization, so much larger depolarizations are required for channel activation.^[4]

References

^ ^a ^b www.sigmaaldrich.com
^ Lampe R.A. et al. Isolation and pharmacological characterization of omega-grammotoxin SIA, a novel peptide inhibitor of neuronal voltage-sensitive calcium channel responses. Mol Pharmacol. 1993 Aug;44(2):451-60 [1]
^ Takeuchi K. et al. Solution Structure of v-Grammotoxin SIA, A Gating Modifier of P/Q and N-type Ca21 Channel. J. Mol. Biol. 2002, 321: 517–526 [2] Archived 2015-02-13 at the Wayback Machine
^ Stefan I. McDonough et al. Voltage-Dependent Inhibition of N- and P-Type Calcium Channels by the Peptide Toxin v-Grammotoxin-SIA. Molecular pharmacology, 1997 52:1095–1104.[3] Archived 2015-02-13 at the Wayback Machine

[sigmaaldrich-1] www.sigmaaldrich.com

[2] Lampe R.A. et al. Isolation and pharmacological characterization of omega-grammotoxin SIA, a novel peptide inhibitor of neuronal voltage-sensitive calcium channel responses. Mol Pharmacol. 1993 Aug;44(2):451-60 [1]

[3] Takeuchi K. et al. Solution Structure of v-Grammotoxin SIA, A Gating Modifier of P/Q and N-type Ca21 Channel. J. Mol. Biol. 2002, 321: 517–526 [2] Archived 2015-02-13 at the Wayback Machine

[4] Stefan I. McDonough et al. Voltage-Dependent Inhibition of N- and P-Type Calcium Channels by the Peptide Toxin v-Grammotoxin-SIA. Molecular pharmacology, 1997 52:1095–1104.[3] Archived 2015-02-13 at the Wayback Machine

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