Imperatoxin I (IpTx) is a

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

toxin derived from the venom of the African scorpion ''

Pandinus imperator The emperor scorpion, ''Pandinus imperator'', is a species of scorpion native to rainforests and savannas in West Africa. It is one of the largest scorpions in the world and lives for 6–8 years. Its body is black, but like other scorpions it ...

''. There are two subtypes of this toxin: *Imperatoxin A (activator): a peptide

toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849– ...

which enhances the influx of Ca²⁺ from the

sarcoplasmatic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

into the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

. *Imperatoxin I (inhibitor): a peptide toxin which decreases the influx of Ca²⁺ from the sarcoplasmatic reticulum into the cell.

Imperatoxin A

The toxin comes from the venom of the African scorpion ''

''. The structure of IpTx_a consists of: *33

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

peptide (sequence GDCLPHLKRCKADNDCCGKKCKRRGTNAEKRCR, disulfide bonds Cys3-Cys17, Cys10-Cys21, Cys16-Cys32). *the formula is C₁₄₈H₂₆₀N₅₈O₄₅S₆. *shares the structure and function of the dihydropiridine receptor ( DHPR). It corresponds to the II-III loop of the α1s

subunit Subunit may refer to: *Subunit HIV vaccine, a class of HIV vaccine *Protein subunit, a protein molecule that assembles with other protein molecules *Monomer, a molecule that may bind chemically to other molecules to form a polymer *Sub-subunit, a ...

. *three

cysteine Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile. When present as a deprotonated catalytic residue, sometime ...

residues that form disulfide bridges to stabilize the three-dimensional structure. The

molecular A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioche ...

weight of the toxin is 3.7

kDa The dalton or unified atomic mass unit (symbols: Da or u) is a non-SI unit of mass widely used in physics and chemistry. It is defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at ...

. IpTx_a acts on the Ryanodine receptors (RyR), which are intracellular Ca²⁺ release channels mainly known for their role in regulating Ca²⁺ release from the

of striated

muscles Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle ...

. The peptide acts better on RyR type 1 than on type 3. RyR type 2 seems to be insensitive to IpTx_a. The part of the peptide that looks like the II-III loop of the (DHPR) binds directly to RyR and enhances ryanodine binding to trigger Ca²⁺ release.

Imperatoxin I

The toxin comes from the venom of the African scorpion ''

''. The structure of IpTx_i consists of: *Two polypeptides. A large

of 104

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

s (sequence TMWGTKWCGSGNEATDISELGYWSNLDSCCRTHDHCDNIPSGQTKYGLTNEGKYTMMNCKCETAFEQCLRNVTGGMEGPAAGFVRKTYFDLYGNGCYNVQCPSQ) and a smaller one of 27 amino acids (sequence SEECPDGVATYTGEAGYGAWAINKLNG). *Subunits are linked by a disulfide bond. *Phospholipase A2 (

PLA2 The enzyme phospholipase A2 (EC 3.1.1.4, PLA2, systematic name phosphatidylcholine 2-acylhydrolase) catalyse the cleavage of fatty acids in position 2 of phospholipids, hydrolyzing the bond between the second fatty acid “tail” and the glycer ...

) activity on the large subunit. The

weight of the toxin is 15

. Like IpTx_a, IpTx_i acts on RyR. When an action potential reaches the muscle, RyR channels open and Ca²⁺ becomes available in the cell to induce contraction. The presence of Ca²⁺ induces the large subunit of IpTx_i to

hydrolyze Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysis ...

the Sn2 fatty acyl bond from the membrane of the sarcoplasmatic reticulum. This process is executed by

activity. The freed fatty acids bind to the RyR itself or to a closely associated protein linked to gating. Binding of the RyR induces blocking of the channel. When the concentration of free fatty acids is low there will be an incomplete block of RyR; higher concentrations will give a complete block. Because IpTx_i also works on the RyR channels of the

heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide t ...

muscles, it could potentially be used as a drug against

arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...

. This has not yet been proven, and must be studied ''in vivo'' first.

References

{{Toxins Ion channel toxins Scorpion toxins