Maurotoxin
This article includes a
disulfide bridges in yellow. Compare the disulfide bond connectivity to HsTx1 below.
Maurotoxin (abbreviated MTX) 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. ChemistryMaurotoxin is a peptide of 34 disulfide bridges (Cys3-Cys24, Cys9-Cys29, Cys13-Cys19, Cys31-Cys34), 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 .
TargetScorpion toxins constitute the largest group of potassium (K+) channel blockers and are useful pharmacological probes to investigate ion channels and their functions. Maurotoxin (MTX) blocks various K+ -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+ (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 immunosuppressants for the treatment of autoimmune disorders (such as rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis).
Mode of actionMTX occludes the pore region of various potassium channels (Kv1.2, IKCa1, Kv1.3) by establishing strong interactions between its 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.
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