Abstract
Animal venom (e.g., scorpion) is a rich source of various protein and peptide toxins with diverse physio-/pharmaco-logical activities, which generally exert their action via target-specific modulation of different ion channel functions. Scorpion venoms are among the most widely-known source of peptidyl neurotoxins used for callipering different ion channels, such as; Na+, K+, Ca+, Cl−, etc. A new peptide of the chlorotoxin family (i.e., Bs-Tx7) has been isolated, sequenced and synthesized from scorpion Buthus sindicus (family Buthidae) venom. This peptide demonstrates 66% with chlorotoxin (ClTx) and 82% with CFTR channel inhibitor (GaTx1) sequence identities reported from Leiurus quinquestriatus hebraeus venom. The toxin has a molecular mass of 3821 Da and possesses four intra-chain disulphide bonds. Amino acid sequence analysis of Bs-Tx7 revealed the presence of a scissile peptide bond (i.e., Gly-Ile) for human MMP2, whose activity is increased in the case of tumour malignancy. The effect of hMMP2 on Bs-Tx7, or vice versa, observed using the FRET peptide substrate with methoxycoumarin (Mca)/dinitrophenyl (Dnp) as fluorophore/quencher, designed and synthesized to obtain the lowest Km value for this substrate, showed approximately a 60% increase in the activity of hMMP2 upon incubation of Bs-Tx7 with the enzyme at a micromolar concentration (4 µM), indicating the importance of this toxin in diseases associated with decreased MMP2 activity.
Highlights
Scorpions, the most ancient arthropods on Earth, can be divided phylogenetically into 18 distinct families consisting of more than 1500 species
A close sequence and structural comparison (Figure 5a) revealed the presence of a scissile peptide bond (i.e., Gly-Ile) for human MMP2, whose activity is increased in the case of tumour malignancy
The work described here and in previous reports provides a molecular basis for the diversity of the chlorotoxin family of peptides from scorpion venoms
Summary
The most ancient arthropods on Earth, can be divided phylogenetically into 18 distinct families consisting of more than 1500 species. Scorpionida) possess a venom apparatus made up of a vesicle holding a pair of venom glands connected to the telson, which is used for injecting the venom. At least thirty species have been identified as potentially toxic to humans [1]. The main venomous families are Buthidae (the largest family with 82 genera and 773 species) and Chactidae (12 genera and 152 species). The venom produced by these scorpions is a complex cocktail of protein and peptide toxins targeting ion channel functions of excitable and non-excitable cells [2,3]. The most remarkable feature is the presence of a large number
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