Structure-Function Relationship of a Novel MTX-like Peptide (MTX1) Isolated and Characterized from the Venom of the Scorpion .

Maurotoxin (MTX) is a 34-residue peptide from venom. It is reticulated by four disulfide bridges with a unique arrangement compared to other scorpion toxins that target potassium (K) channels. Structure-activity relationship studies have not been well performed for this toxin family. The screening of venom was performed by different steps of fractionation, followed by the ELISA test, using MTX antibodies, to isolate an MTX-like peptide. In vitro, in vivo and computational studies were performed to study the structure-activity relationship of the new isolated peptide. We isolated a new peptide designated MTX1, structurally related to MTX. It demonstrated toxicity on mice eight times more effectively than MTX. MTX1 blocks the Kv1.2 and Kv1.3 channels, expressed in Xenopus oocytes, with IC values of 0.26 and 180 nM, respectively. Moreover, MTX1 competitively interacts with both I-apamin (IC = 1.7 nM) and I-charybdotoxin (IC = 5 nM) for binding to rat brain synaptosomes. Despite its high sequence similarity (85%) to MTX, MTX1 exhibits a higher binding affinity towards the Kv1.2 and SKCa channels. Computational analysis highlights the significance of specific residues in the β-sheet region, particularly the R27, in enhancing the binding affinity of MTX1 towards the Kv1.2 and SKCa channels.