A novel peptide, scorpine, was isolated from the venom of the scorpion Pandinus imperator, with anti-bacterial activity and a potent inhibitory effect on the ookinete (ED 50 0.7 W WM) and gamete (ED 50 10 W WM) stages of Plasmodium berghei development. It has 75 amino acids, three disulfide bridges with a molecular mass of 8350 Da. Scorpine has a unique amino acid sequence, similar only to some cecropins in its N-terminal segment and to some defensins in its C-terminal region. Its gene was cloned from a cDNA library.z 2000 Federation of European Biochemical Societies.

A new antimicrobial peptide, hadrurin, was isolated from the venom of the Mexican scorpion Hadrurus aztecus, by gel filtration on a Sephadex G-50 column, followed by high performance liquid chromatography. It is a basic peptide composed of 41 amino-acid residues with a molecular mass of 4436 Da, and contains no cysteines. A model of the three-dimensional folding of hadrurin is compatible with that of an amphipatic molecule with two a-helical segments. Hadrurin demonstrates antimicrobial activity at low micromolar concentration, inhibiting the growth of bacteria such as: Salmonella thyphi, Klebsiella pneumoniae, Enterococcus cloacae, Pseudomonas aeruginosa, Escherichia coli and Serratia marscences. It also shows cytolytic activity when tested in human erythrocytes. Hadrurin and two analogs (C-terminal amidated, and all d-enantiomer) were chemically synthesized. They were used to study the possible molecular mechanism of action by testing their ability to dissipate the diffusion potential of liposomes of different compositions. The results obtained indicate that there are no specific receptor molecules for the action of hadrurin, and the most probable mechanism is through a membrane destabilization activity. It is surmised that hadrurin is used by the scorpion as both an attack and defense element against its prey and putative invasive microorganisms. It is a unique peptide among all known antimicrobial peptides described, only partially similar to the N-terminal segment of gaegurin 4 and brevinin 2e, isolated from frog skin. It would certainly be a model molecule for studying new antibiotic activities and peptide±lipid interactions. . Most of these peptides share some common characteristics such as their low molecular mass (2±5 kDa), the presence of multiple lysine and arginine residues, and their amphipatic nature. Their site of action is the cytoplasmic membrane, where they destabilize its lipid package and produce transient channels (reviewed in [26±28]). However, it seems that the primary action of some of them, such as PR39 [29,30], is not directed towards the membrane, and it is believed that for plant defensins there exists a receptor [31,32];. Although the minimal inhibitory concentrations (1±50 mm) of these molecules are high in comparison to other antibiotics, their broad activity spectra and speed of action makes them good candidates for delivering drugs, and a number of possible applications have already been described (reviewed in [33]).Scorpion venom has been traditionally studied for the presence of neurotoxins that affect ion channels: sodium, potassium, calcium and chloride [34], and very little is known about peptides with different activity. Antimicrobial peptides have been isolated from the venom of spider [35], hornet [23] and bee [16].This communication reports the isolation of a novel antibacterial and cytolytic peptide constitutively present in the venom of the scorpion Hadrurus aztecus. It has a unique sequence, quite different from other antimicrobial peptides isolated from the hemolymp...

We present an in-depth analysis of the structural and functional properties of Imperatoxin I (IpTx i ), an ϳ15-kDa protein from the venom of the scorpion Pandinus imperator that inhibits Ca 2؉ release channel/ryanodine receptor (RyR) activity (Valdivia, H. H., Kirby, M. S., Lederer, W. J., and Coronado, R. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 12185-12189). A cDNA library was prepared from the venomous glands of this scorpion and used to clone the gene encoding IpTx i . From a single continuous messenger RNA, the information coding for the toxin is translated into two mature polypeptide subunits after elimination of a basic pentapeptide. The IpTx i dimer consists of a large subunit (104-amino acid residues) with phospholipase A 2 (PLA 2 ) activity covalently linked by a disulfide bond to a smaller (27 amino acid residues), structurally unrelated subunit. Thus, IpTx i is a heterodimeric protein with lipolytic action, a property that is only shared with ␤-bungarotoxins, a group of neurotoxins from snake venoms. The enzymatic subunit of IpTx i is highly homologous to PLA 2 from bee (Apis mellifera) and lizard (Heloderma horridum) venoms. The small subunit has no significant similarity to any other known peptide, including members of the Kunitz protease inhibitors superfamily that target the lipolytic effect of ␤-bungarotoxins. A synthetic peptide with amino acid sequence identical to that of the small subunit failed to inhibit RyR. On the other hand, treatment of IpTx i with p-bromophenacylbromide, a specific inhibitor of PLA 2 activity, greatly reduced the capacity of IpTx i to inhibit RyRs. These results suggested that a lipid product of PLA 2 activity, more than a direct IpTx i -RyR interaction, was responsible for RyR inhibition.

Calcins are a new and expanding family of ryanodine receptor agonists found in scorpion venom. Xiao and colleagues characterize the structure–function relationships of all known calcins and show both similarities and differences in their form and function.