Maurotoxin

Maurotoxin is a peptide toxin from the venom of the Tunisian chactoid scorpion 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].

Chemistry

Maurotoxin is a peptide of 34 amino acids cross-linked by four disulfide bridges, with an atypical pattern of organization compared with other scorpion toxins; this unusual pairing of cysteine residues may be mediated by the presence of adjacent prolines. The peptide contains an alpha helix linked by two disulfide bridges to a two-stranded antiparallel beta sheet.

Target

Scorpion toxins constitute the largest group of potassium channel blockers and are useful pharmacological probes to investigate ion channels and their functions.
Maurotoxin blocks various K⁺ -channels:

Apamin-sensitive small conductance Ca²⁺ - activated K⁺ channels
Intermediate conductance Ca²⁺ - activated K⁺ channels
Several types of voltage-gated potassium channels

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⁺ and K⁺ channel scorpion toxin families.
The intermediate conductance Ca²⁺-activated K⁺ channel is present in peripheral tissues, including secretory epithelia and blood cells. 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 proliferation. Thus IK blockers could be potential immunosuppressants for the treatment of autoimmune disorders.

Mode of action

MTX occludes the pore region of various potassium channels by establishing strong interactions between its lysine-23 residue and the glycine-tyrosine-glycine-aspartate 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.