# Agitoxin
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> Source: https://en.wikipedia.org/wiki/Agitoxin
> Source revision: 1352651225
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{{Infobox protein family
| Symbol = Toxin_2
| Name = Scorpion short toxin
| image = 1agt.png
| width =
| caption = Agitoxin-2. Disulphide bonds are highlighted. [PDB](/source/Protein_Data_Bank) {{PDBe|1agt}} [{{cite journal | vauthors = Krezel AM, Kasibhatla C, Hidalgo P, MacKinnon R, Wagner G | title = Solution structure of the potassium channel inhibitor agitoxin 2: caliper for probing channel geometry | journal = Protein Science | volume = 4 | issue = 8 | pages = 1478–89 | date = August 1995 | pmid = 8520473 | pmc = 2143198 | doi = 10.1002/pro.5560040805 }}]
| Pfam = PF00451
| Pfam_clan = CL0054
| InterPro = IPR001947
| SMART =
| PROSITE = PDOC00875
| MEROPS =
| SCOP =
| OPM family = 58
| OPM protein = 3odv
| CAZy =
| CDD =
}}
'''Agitoxin''' is a [toxin](/source/toxin) found in the [venom](/source/venom) of the scorpion ''[Leiurus quinquestriatus hebraeus](/source/Deathstalker)'' (yellow scorpion). Other [toxins](/source/toxins) found in this species include [charybdotoxin](/source/charybdotoxin) (CTX). CTX is a close homologue of Agitoxin.[{{cite journal | vauthors = Bontems F, Roumestand C, Gilquin B, Ménez A, Toma F | title = Refined structure of charybdotoxin: common motifs in scorpion toxins and insect defensins | journal = Science | volume = 254 | issue = 5037 | pages = 1521–3 | date = December 1991 | pmid = 1720574 | doi = 10.1126/science.1720574 | bibcode = 1991Sci...254.1521B }}]
== Structure ==
Agitoxin can be purified using [HPLC](/source/High-performance_liquid_chromatography) techniques.
'''Primary structure:'''
Three types of agitoxin can be distinguished, each identified as comprising 38 [amino acid](/source/amino_acid)s. They are highly homologous, differing only in the identity of the residues at positions 7, 15, 29 and 31.
Alignment of Agitoxins. Disulphide bonds are indicated beneath the alignment.
*'''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 (GVPINVKCTGSPQCLKPCKDAGMRFGKCINGKCHCTPK, [molecular weight](/source/molecular_weight) = 4014.87 [Da](/source/Atomic_mass_unit), 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 (GVPINVSCTGSPQCIKPCKDAGMRFGKCMNRKCHCTPK, 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 (GVPINVPCTGSPQCIKPCKDAGMRFGKCMNRKCHCTPK, molecular weight = 4100.98 Da, molecular formula = C171H280N54O47S8, [CAS Number](/source/CAS_registry_number) 155646-23-4)
'''Secondary and tertiary structure:'''
Agitoxin consists of a triple-stranded antiparallel [beta-sheet](/source/Beta_sheet) in which the C-terminal strand sits in the centre of the sheet, and a single [alpha-helix](/source/alpha-helix) covering one face of the beta-sheet (see image on the right). The [cysteine side chains](/source/cysteine) connect the beta-sheet and the helix via [disulphide bonds](/source/disulphide_bonds) to form the core of the molecule.
The fold of agitoxin is homologous to the previously determined folds of scorpion venom toxins, classified as 'Scorpion short toxins' by [Pfam](/source/Pfam).
This fold, and the location of the disulphide bonds, are a shared element between toxins stemming from arthropods. The structure of agitoxin-2, has been determined by NMR.[{{cite journal | vauthors = Eriksson MA, Roux B | title = Modeling the structure of agitoxin in complex with the Shaker K+ channel: a computational approach based on experimental distance restraints extracted from thermodynamic mutant cycles | journal = Biophysical Journal | volume = 83 | issue = 5 | pages = 2595–609 | date = November 2002 | pmid = 12414693 | pmc = 1302345 | doi = 10.1016/S0006-3495(02)75270-3 | bibcode = 2002BpJ....83.2595E }}] AgTx2 has been found to undergo conformational changes when bound to the 'Shaker K' channel which suggests the [induced fit](/source/induced_fit) model may be present in toxin-channel interaction. This mode of interaction goes along with and explains the flexible side chains.[{{cite journal | vauthors = Lin YW, Wang KJ, Lei HY, Lin YS, Yeh TM, Liu HS, Liu CC, Chen SH | title = Virus replication and cytokine production in dengue virus-infected human B lymphocytes | journal = Journal of Virology | volume = 76 | issue = 23 | pages = 12242–9 | date = December 2002 | pmid = 12414963 | pmc = 136880 | doi = 10.1128/JVI.76.23.12242-12249.2002 }}] The [amino acid](/source/amino_acid) make up of the toxin determines the way each interacts with [Shaker](/source/Shaker_(gene)) K channels.[{{cite journal | vauthors = Gao YD, Garcia ML | title = Interaction of agitoxin2, charybdotoxin, and iberiotoxin with potassium channels: selectivity between voltage-gated and Maxi-K channels | journal = Proteins | volume = 52 | issue = 2 | pages = 146–54 | date = August 2003 | pmid = 12833539 | doi = 10.1002/prot.10341 | s2cid = 7136604 }}] Important stabilizing hydrogen bonding between various residues on the AgTx2 and the subunits of the channel hold the toxin-channel complex together. Mutations in Arg24Ala, Lys27Met, and Asn30Ala increased the dissociation, or break-down, of the complex, suggesting they all play important roles in holding the toxin on the channel.