Tamapin
Encyclopedia
Tamapin is a toxin from the Indian Red Scorpion (Mesobuthus tamalus), which is a selective and potent blocker of SK2 channels.
. Its sequence similarity to other toxins that can compete with the binding site of apamin
is much lower. It is 31 amino acids long and its weight is 3458 Daltons
. Its amino acid sequence is given in Table 1.
Table 1 Amino-acid sequence of tamapin
Tamapin has been isolated via detection of the apamin-competing fracture of the venom from the scorpion via a Sephadex
G-50 size exclusion chromatography
, followed by high performance liquid chromatography
(HPLC).
An isoform of tamapin, tamapin-2, has been found, in which the tyrosine is replaced by a histadine. Tamapin-2 can also compete very effectively with apamin for binding to synaptosomes.
toxin
blocks SK2 channels with selectivity for SK2 versus SK1 channels in a largely reversible manner. Despite completely different sequences, Apamin
(a bee venom toxin) and Tamapin share at least in part, the same binding sites on rat brain synaptosomes. Cloned SK2 are most sensitive for Apamin
in binding assays and physiological recordings. However, Tamapin displaces Apamin in binding assays and is therefore a stronger toxin
with respect to Apamin. SK 1 and SK 3 are only affected with a high concentration of Tapamin and therefor this toxin inhibits SK2 with the highest affinity, SK3 intermediate and the lowest affinity for SK1 channels. A less closely related member of the SK channels is the intermediate conductance calcium activated potassium channel SK4, also known as IK1, which is not sensitive to Apamin and is also not affected by Tapamin. The same applies to voltage dependent potassium channels; the block of SK2-mediated currents is not voltage dependent. This specific channel block evokes a reduction in the small conductance calcium-dependent potassium channels current.
contains highly specific potassium channel blockers such as iberiotoxin
, which is a highly specific blocker of the high conductance calcium activated potassium channel, and tamulustoxin.
Chemical structure & methods of isolation
Tamapin belongs to short-chain scorpion toxin subfamily 5, together with PO5 and ScyllatoxinScyllatoxin
Scyllatoxin is a toxin, from the scorpion Leiurus quinquestriatus hebraeus, which blocks small-conductance Ca2+-activated K+ channels.- Source :...
. Its sequence similarity to other toxins that can compete with the binding site of apamin
Apamin
Apamin is an 18 amino acid peptide neurotoxin found in apitoxin . It selectively blocks SK channels, a type of Ca2+-activated K+ channel expressed in the central nervous system and smooth muscle...
is much lower. It is 31 amino acids long and its weight is 3458 Daltons
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...
. Its amino acid sequence is given in Table 1.
| Ala | Phe | Cys | Asn | Leu | Arg | Arg | Cys | Glu | Leu | Ser | Cys | Arg | Ser | Leu | Gly |
| Leu | Leu | Gly | Lys | Cys | Ile | Gly | Glu | Glu | Cys | Lys | Cys | Val | Pro | Tyr |
Table 1 Amino-acid sequence of tamapin
Tamapin has been isolated via detection of the apamin-competing fracture of the venom from the scorpion via a Sephadex
Sephadex
Sephadex is a trademark for cross-linked dextran gel used for gel filtration. It was launched by Pharmacia in 1959, after development work by Jerker Porath and Per Flodin. The name is derived from separation Pharmacia dextran. It is normally manufactured in a bead form and most commonly used for...
G-50 size exclusion chromatography
Size exclusion chromatography
Size-exclusion chromatography is a chromatographic method in which molecules in solution are separated by their size, and in some cases molecular weight . It is usually applied to large molecules or macromolecular complexes such as proteins and industrial polymers...
, followed by high performance liquid chromatography
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...
(HPLC).
An isoform of tamapin, tamapin-2, has been found, in which the tyrosine is replaced by a histadine. Tamapin-2 can also compete very effectively with apamin for binding to synaptosomes.
Target and mode of action
The target of Tamapin is the small conductance calcium-dependent potassium (SK) channel. This scorpionScorpion
Scorpions are predatory arthropod animals of the order Scorpiones within the class Arachnida. They have eight legs and are easily recognized by the pair of grasping claws and the narrow, segmented tail, often carried in a characteristic forward curve over the back, ending with a venomous stinger...
toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
blocks SK2 channels with selectivity for SK2 versus SK1 channels in a largely reversible manner. Despite completely different sequences, Apamin
Apamin
Apamin is an 18 amino acid peptide neurotoxin found in apitoxin . It selectively blocks SK channels, a type of Ca2+-activated K+ channel expressed in the central nervous system and smooth muscle...
(a bee venom toxin) and Tamapin share at least in part, the same binding sites on rat brain synaptosomes. Cloned SK2 are most sensitive for Apamin
Apamin
Apamin is an 18 amino acid peptide neurotoxin found in apitoxin . It selectively blocks SK channels, a type of Ca2+-activated K+ channel expressed in the central nervous system and smooth muscle...
in binding assays and physiological recordings. However, Tamapin displaces Apamin in binding assays and is therefore a stronger toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
with respect to Apamin. SK 1 and SK 3 are only affected with a high concentration of Tapamin and therefor this toxin inhibits SK2 with the highest affinity, SK3 intermediate and the lowest affinity for SK1 channels. A less closely related member of the SK channels is the intermediate conductance calcium activated potassium channel SK4, also known as IK1, which is not sensitive to Apamin and is also not affected by Tapamin. The same applies to voltage dependent potassium channels; the block of SK2-mediated currents is not voltage dependent. This specific channel block evokes a reduction in the small conductance calcium-dependent potassium channels current.
Toxicity
Previous studies showed that the effect of tamapin is largely reversible and depends on time and concentration. The Indian red scorpion (Mesobuthus tamulus) causes a large number of deaths annually especially among young children. Its venomVenom
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...
contains highly specific potassium channel blockers such as iberiotoxin
Iberiotoxin
Iberiotoxin is an ion channel toxin purified from the Eastern Indian red scorpion Buthus tamulus.Iberiotoxin selectively inhibits the current through large-conductance calcium-activated potassium channels.- Chemistry :...
, which is a highly specific blocker of the high conductance calcium activated potassium channel, and tamulustoxin.