Maurotoxin

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Maurotoxin

Maurotoxin (abbreviated MTX) is a peptide

Peptide

Peptides are short polymers formed from the linking, in a defined order, of a-amino acids. The link between one amino acid residue and the next is known as an amide chemical bond or a peptide bond....
toxin

Toxin

A toxin is a poisonous substance produced by living cells or organisms. For a toxic substance not produced by living organisms, "toxicant" is the more appropriate term, and "toxics" is an acceptable plural....
from the venom of the Tunisian chactoid scorpion

Scorpion

Scorpions are any arachnid of the order Scorpionida. They are members of the order Scorpiones within the class Arachnida. There are about 2,000 species of scorpions, found widely distributed south of about Latitude, except New Zealand and Antarctica....
Scorpio maurus palmatus, from which it was first isolated and from which the chemical gets its name. It acts by blocking several types of voltage-gated potassium channel

Voltage-gated potassium channel

Voltage-gated potassium channels are potassium channel and Voltage-gated ion channel in the cell's membrane potential. They play a crucial role during action potentials in returning the depolarized cell to a resting state....
.

otoxin is a peptide of 34 amino acid

Amino acid

In chemistry, an amino acid is a molecule containing both amine and carboxyl functional groups. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H2NCHRCOOH, where R is an organic substituent....
s cross-linked by four disulfide bridges, with an atypical pattern of organization compared with other scorpion toxins; this unusual pairing of cysteine

Cysteine

Cysteine is an a-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that humans can synthesize it....
residues may be mediated by the presence of adjacent proline

Proline

Proline is an a-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that humans can synthesize it....
s.

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Encyclopedia

Maurotoxin (abbreviated MTX) is a peptide

Peptide

Toxin

Scorpion

Voltage-gated potassium channel

Chemistry

Maurotoxin is a peptide of 34 amino acid

Amino acid

Cysteine

Proline

Proline is an a-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that humans can synthesize it....
s. The peptide contains an alpha helix

Alpha helix

A common motif in the secondary structure of proteins, the alpha helix is a right- or left-handed coiled conformation, resembling a spring , in which every backbone amino group donates a hydrogen bond to the backbone carbonyl group of the amino acid four residues earlier ....
linked by two disulfide bridges to a two-stranded antiparallel beta sheet

Beta sheet

The ? sheet is the second form of regular secondary structure in proteins consisting of beta strands connected laterally by three or more hydrogen bonds, forming a generally twisted, pleated sheet ....
.

Target

Scorpion toxins constitute the largest group of potassium

Potassium

Potassium is a chemical element. It has the symbol K , atomic number 19, and atomic mass 39.0983. Potassium was first isolated from potash, hence the name....
(K⁺) channel blockers and are useful pharmacological probes to investigate ion channels and their functions.

Maurotoxin (MTX) blocks various K⁺ -channels:

Apamin
Apamin

Apamin is a neurotoxin which selectively blocks SK channels, a type of Ca activated K channel expressed in the central nervous system. The final 18 amino acid polypeptide is a component of apitoxin ....
-sensitive small conductance Ca²⁺
Calcium

Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft grey alkaline earth metal, and is the fifth most abundant element by mass in the earth's Crust ....
- activated K⁺
Potassium

Potassium is a chemical element. It has the symbol K , atomic number 19, and atomic mass 39.0983. Potassium was first isolated from potash, hence the name....
channels (SK)
Intermediate conductance Ca²⁺ - activated K⁺ channels (IK)
Several types of voltage-gated potassium channel
Voltage-gated potassium channel

Voltage-gated potassium channels are potassium channel and Voltage-gated ion channel in the cell's membrane potential. They play a crucial role during action potentials in returning the depolarized cell to a resting state....
s (Kv1.1, Kv1.2, Kv1.3 and shaker B)

The structural and pharmacological features of MTX suggest that MTX belongs to a new class of natural K⁺ channel blockers structurally intermediate between the Na⁺ (60–70 residues and four disulfide bridges) and K⁺ channel scorpion toxin families (less than 40 residues and three disulfide bridges).

The intermediate conductance Ca²⁺-activated K⁺ (IK) channel is present in peripheral tissues, including secretory epithelia and blood cell

Blood cell

A blood cell is any cell of any type normally found in blood. In mammals, these fall into three general categories:*Red blood cells*White blood cells...
s. An important physiological role of the IK channel is to help maintain large electrical gradients for the sustained transport of ions such as Ca²⁺ that controls T lymphocyte (T cell) proliferation. Thus IK blockers could be potential immunosuppressant

Immunosuppressant

An immunosuppressant is a substance that performs immunosuppression of the immune system. They may either be exogenous, as immunosuppressive drugs, or endogenous, as e....
s for the treatment of autoimmune disorders (such as rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis).

Mode of action

MTX occludes the pore region of various potassium channels (Kv1.2, IKCa1, Kv1.3) by establishing strong interactions between its lysine

Lysine

Lysine is an a-amino acid with the chemical formula HO2CCH4NH2. This amino acid is an essential amino acid, which means that humans cannot synthesize it....
-23 residue and the glycine

Glycine

Glycine is the organic compound with the chemical formula NH2CH2COOH. It is the smallest of the 20 amino acids commonly found in proteins, coded by codons GGU, GGC, GGA and GGG....
-tyrosine

Tyrosine

Tyrosine or 4-hydroxyphenylalanine, is one of the 20 amino acids that are used by cell to protein biosynthesis proteins. This is a non-essential amino acid and it is found in casein....
-glycine

Glycine

Glycine is the organic compound with the chemical formula NH2CH2COOH. It is the smallest of the 20 amino acids commonly found in proteins, coded by codons GGU, GGC, GGA and GGG....
-aspartate (GYGD) motif of the channel. MTX thus blocks the channels by binding in the external vestibule of the pore to block the ion conduction pathway. Although Kv1.1, Kv1.2, and Kv1.3 have a very similar pore structure, they display different pharmacological sensitivity to MTX.