grammotoxin
{{Short description|Toxin}}
[[File:1koz.jpg|thumb|Solution structure of omega-grammotoxin SIA. PDB entry {{PDBe|1koz}}{{Cite journal
| doi = 10.1016/S0022-2836(02)00595-8
| last1 = Takeuchi | first1 = K.
| last2 = Park | first2 = E.
| last3 = Lee | first3 = C.
| last4 = Kim | first4 = J.
| last5 = Takahashi | first5 = H.
| last6 = Swartz | first6 = K.
| last7 = Shimada | first7 = I.
| title = Solution structure of omega-grammotoxin SIA, a gating modifier of P/Q and N-type Ca(2+) channel
| journal = Journal of Molecular Biology
| volume = 321
| issue = 3
| pages = 517–526
| year = 2002
| pmid = 12162963
}}]]
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.
Its chemical formula is: C177H268N52O50S6[http://www.sigmaaldrich.com/catalog/search/ProductDetail?ProdNo=G2795&Brand=SIGMA ω-Grammotoxin SIA from Grammostola spatulata venom, ≥98% (HPLC)]
Grammotoxin can be purified from Grammostola spatulata venom by reverse phase high performance liquid chromatography.{{Cite journal
| last1 = Lampe | first1 = R. A.
| last2 = Defeo | first2 = P. A.
| last3 = Davison | first3 = M. D.
| last4 = Young | first4 = J.
| last5 = Herman | first5 = J. L.
| last6 = Spreen | first6 = R. C.
| last7 = Horn | first7 = M. B.
| last8 = Mangano | first8 = T. J.
| last9 = Keith | first9 = R. A.
| title = Isolation and pharmacological characterization of omega-grammotoxin SIA, a novel peptide inhibitor of neuronal voltage-sensitive calcium channel responses
| journal = Molecular Pharmacology
| volume = 44
| issue = 2
| pages = 451–460
| year = 1993
| pmid = 8394998
}}
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.{{Cite journal
| last1 = McDonough | first1 = S. I.
| last2 = Lampe | first2 = R. A.
| last3 = Keith | first3 = R. A.
| last4 = Bean | first4 = B. P.
| title = Voltage-dependent inhibition of N- and P-type calcium channels by the peptide toxin omega-grammotoxin-SIA
| journal = Molecular Pharmacology
| volume = 52
| issue = 6
| pages = 1095–1104
| year = 1997
| doi = 10.1124/mol.52.6.1095
| pmid = 9415720
}} 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. Grammotoxin also binds to potassium channels but with lower affinity than to the calcium channels.