Agitoxin
Encyclopedia
Agitoxin is a toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...

 found in the venom
Venom
Venom is the general term referring to any variety of toxins used by certain types of animals that inject it into their victims by the means of a bite or a sting...

 of the scorpion Leiurus quinquestriatus herbraeus
Deathstalker
The deathstalker , is a species of scorpion, a member of the Buthidae family. It is also known as Palestine yellow scorpion, Omdurman scorpion, Israeli desert scorpion and numerous other colloquial names, which generally originate from the commercial captive trade of the animal...

(yellow scorpion).

Agitoxin binds to the Shaker
Shaker gene
The shaker gene, when mutated, causes a variety of atypical behaviors in the fruit fly, Drosophila melanogaster. Under ether anesthesia, the fly’s legs will shake ; even when the fly is unanaesthetized, it will exhibit aberrant movements...

 K+ channel in Drosophila
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...

as well as to its mammalian homologue. It blocks this channel by binding with high affinity (Kd < 1 nmol/L
Litér
- External links :*...

) to its external vestibule.

Agitoxin can be purified using HPLC
High-performance liquid chromatography
High-performance liquid chromatography , HPLC, is a chromatographic technique that can separate a mixture of compounds and is used in biochemistry and analytical chemistry to identify, quantify and purify the individual components of the mixture.HPLC typically utilizes different types of stationary...

 techniques. Its structure consists of a triple-stranded antiparallel beta-sheet
Beta sheet
The β sheet is the second form of regular secondary structure in proteins, only somewhat less common than the alpha helix. Beta sheets consist of beta strands connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet...

 and a single helix covering one face of the beta-sheet. The cysteine side chains
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...

 connect the beta-sheet and the helix form to the core of the molecule. The fold
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....

 of agitoxin is homologous to the previously determined folds of scorpion venom toxins.

Three types of agitoxin can be distinguished, each identified as comprising 38 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 (cysteine bonds not shown):
  • Agitoxin-1 Gly-Val-Pro-Ile-Asn-Val-Lys-Cys-Thr-Gly-Ser-Pro-Gln-Cys-Leu-Lys-Pro-Cys-Lys-Asp-Ala-Gly-Met-Arg-Phe-Gly-Lys-Cys-Ile-Asn-Gly-Lys-Cys-His-Cys-Thr-Pro-Lys (molecular weight = 4014.87 Da
    Atomic mass unit
    The unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...

    , molecular formula = C169H278N52O47S7)

  • Agitoxin-2 Gly-Val-Pro-Ile-Asn-Val-Ser-Cys-Thr-Gly-Ser-Pro-Gln-Cys-Ile-Lys-Pro-Cys-Lys-Asp-Ala-Gly-Met-Arg-Phe-Gly-Lys-Cys-Met-Asn-Arg-Lys-Cys-His-Cys-Thr-Pro-Lys (molecular weight = 4090.95 Da, molecular formula = C169H278N54O48S8)

  • Agitoxin-3 Gly-Val-Pro-Ile-Asn-Val-Pro-Cys-Thr-Gly-Ser-Pro-Gln-Cys-Ile-Lys-Pro-Cys-Lys-Asp-Ala-Gly-Met-Arg-Phe-Gly-Lys-Cys-Met-Asn-Arg-Lys-Cys-His-Cys-Thr-Pro-Lys (molecular weight = 4100.98 Da, molecular formula = C171H280N54O47S8, CAS Number
    CAS registry number
    CAS Registry Numbersare unique numerical identifiers assigned by the "Chemical Abstracts Service" toevery chemical described in the...

    155646-23-4)
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