Solution structure of omega-grammotoxin SIA. PDB entry 1koz[1]

Grammotoxin is a toxin in the venom of the tarantula Grammostola spatulata. It is a protein toxin that inhibits P-, Q- and N-type voltage-gated calcium channels (Ca 2+ channels) in neurons. Grammotoxin is also known as omega-grammotoxin SIA.

Chemistry

Grammotoxin is a 36 amino acid protein toxin, with the 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 (DCVRFWGKCSQTSDCCPHLACKSKWPRNICVWDGSV), and disulfide bridges between Cys2-Cys16, Cys9-Cys21 and Cys15-Cys30.

It forms an inhibitor cystine knot motif, common in spider toxins.[1]

Its chemical formula is: C177H268N52O50S6[2]

Grammotoxin can be purified from Grammostola spatulata venom by reverse phase high performance liquid chromatography.[3]

Mode of action

The toxin binding site on the channels has high affinity for the toxins when they are closed and low affinity when channels are activated.[4] As a result, the toxin preferentially binds to the closed channels. It binds at a region which contains the voltage-sensing domains. When bound, the toxin makes it more difficult for channels to be opened by depolarization, so much larger depolarizations are required for channel activation.[4] Grammotoxin also binds to potassium channels but with lower affinity than to the calcium channels.[1]

References

  1. 1 2 3 Takeuchi, K.; Park, E.; Lee, C.; Kim, J.; Takahashi, H.; Swartz, K.; Shimada, I. (2002). "Solution structure of omega-grammotoxin SIA, a gating modifier of P/Q and N-type Ca(2+) channel". Journal of Molecular Biology. 321 (3): 517–526. doi:10.1016/S0022-2836(02)00595-8. PMID 12162963.
  2. ↑ ω-Grammotoxin SIA from Grammostola spatulata venom, ≥98% (HPLC)
  3. ↑ Lampe, R. A.; Defeo, P. A.; Davison, M. D.; Young, J.; Herman, J. L.; Spreen, R. C.; Horn, M. B.; Mangano, T. J.; Keith, R. A. (1993). "Isolation and pharmacological characterization of omega-grammotoxin SIA, a novel peptide inhibitor of neuronal voltage-sensitive calcium channel responses". Molecular Pharmacology. 44 (2): 451–460. PMID 8394998.
  4. 1 2 McDonough, S. I.; Lampe, R. A.; Keith, R. A.; Bean, B. P. (1997). "Voltage-dependent inhibition of N- and P-type calcium channels by the peptide toxin omega-grammotoxin-SIA". Molecular Pharmacology. 52 (6): 1095–1104. doi:10.1124/mol.52.6.1095. PMID 9415720.
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