Slotoxin
Encyclopedia
Slotoxin is a peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...

 from Centruroides noxius Hoffmann scorpion
Scorpion
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...

 venom. It belongs to the short scorpion toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...

 superfamily.

Method of isolation

For isolation of slotoxin, scorpions of the species Centruroides noxius are milked for venom in the laboratory. The crude venom is being dissolved in distilled water and spun. The supernatant is separated. The active fraction is then further separated.

Structure

The 37 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 peptide belongs to the charybdotoxin
Charybdotoxin
Charybdotoxin is a 37 amino acid neurotoxin from the venom of the scorpion Leiurus quinquestriatus hebraeus that blocks calcium-activated potassium channels. This blockade causes hyperexcitability of the nervous system.-Chemical properties:...

 sub-family (αKTx1) and was numbered member 11. αKTx1.11 revealed specificity for mammalian MaxiK channels (hSlo), thus, was named slotoxin.

Targets

Slotoxin reversibly blocks the high conductance calcium-activated potassium channels composed of only α-subunits (Kd
KD
KD may refer to:* Kapal DiRaja, ship prefix used in the Royal Malaysian Navy* Kappa Delta, a National Panhellenic sorority* Katamari Damacy, a video game by Namco* Kawasaki disease* Kentucky Derby* Ketogenic diet...

 = 1.5 nM). Unreversibly blocks the high conductance calcium-activated potassium channels composed of α- and β1-subunits. Unreversibly and weakly blocks the high conductance calcium-activated potassium channels composed of α- and β4-subunits. It shows no activity on other potassium channels.

Mode of action

The positively charged surface (C-terminal) of SloTx has a specific short-range interaction with the negatively charged pore region of potassium-channels leading to channel blockade. Specific hydrophobic residue-residue interactions between SloTx and MaxiK channels may also contribute to toxin-channel interaction. Another region in the potassium channel (flanking the N-terminal of SloTx) is situated in the face opposite to the site of toxin-pore interaction, and might have implications for the modulation of channel blockade by the MaxiK β subunits.
SloTx is suggested to interact with the MaxiK channel pore-forming α-subunit
by blocking the pore via a bimolecular reaction.

Toxicity

The large-conductance voltage and calcium-activated potassium (MaxiK, BK) channels are intrinsic membrane proteins that regulate excitability in a large variety of tissues including brain and smooth muscle
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...

.
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