Imperatoxin I (IpTx) is a

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

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 six to eight years. Its body is black, but like other scorpi ...

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

toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...

which enhances the influx of Ca²⁺ from the sarcoplasmatic reticulum into the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...

. *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 over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

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. *three

cysteine Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...

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

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

weight of the toxin is 3.7 kDa. 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 sarcoplasmatic reticulum of striated

muscles Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...

. 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 subunit of 104

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s (sequence TMWGTKWCGSGNEATDISELGYWSNLDSCCRTHDHCDNIPSGQTKYGLTNEGKYTMMNCKCETAFEQCLRNVTGGMEGPAAGFVRKTYFDLYGNGCYNVQCPSQ) and a smaller one of 27 amino acids (sequence SEECPDGVATYTGEAGYGAWAINKLNG). *Subunits are linked by a disulfide bond. *Phospholipase A2 ( PLA2) activity on the large subunit. The

weight of the toxin is 15 kDa. 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 PLA2 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 (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

muscles, it could potentially be used as a drug against

arrhythmia Arrhythmias, also known as cardiac arrhythmias, are irregularities in the cardiac cycle, heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – ab ...

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

References

{{Toxins Ion channel toxins Scorpion toxins