Na⁺‐channel specific scorpion toxins are peptides of 60–76 amino acid residues in length, tightly bound by four disulfide bridges. The complete amino acid sequence of 85 distinct peptides are presently known. For some toxins, the three‐dimensional structure has been solved by X‐ray diffraction and NMR spectroscopy. A constant structural motif has been found in all of them, consisting of one or two short segments of α‐helix plus a triple‐stranded β‐sheet, connected by variable regions forming loops (turns). Physiological experiments have shown that these toxins are modifiers of the gating mechanism of the Na⁺‐channel function, affecting either the inactivation (α‐toxins) or the activation (β‐toxins) kinetics of the channels. Many functional variations of these peptides have been demonstrated, which include not only the classical α‐ and β‐types, but also the species specificity of their action. There are peptides that bind or affect the function of Na⁺‐channels from different species (mammals, insects or crustaceans) or are toxic to more than one group of animals. Based on functional and structural features of the known toxins, a classification containing 10 different groups of toxins is proposed in this review. Attempts have been made to correlate the presence of certain amino acid residues or ‘active sites’ of these peptides with Na⁺‐channel functions. Segments containing positively charged residues in special locations, such as the five‐residue turn, the turn between the second and the third β‐strands, the C‐terminal residues and a segment of the N‐terminal region from residues 2–11, seems to be implicated in the activity of these toxins. However, the uncertainty, and the limited success obtained in the search for the site through which these peptides bind to the channels, are mainly due to the lack of an easy method for expression of cloned genes to produce a well‐folded, active peptide. Many scorpion toxin coding genes have been obtained from cDNA libraries and from polymerase chain reactions using fragments of scorpion DNAs, as templates. The presence of an intron at the DNA level, situated in the middle of the signal peptide, has been demonstrated.

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 α‐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.

Background: Scorpions like other venomous animals posses a highly specialized organ that produces, secretes and disposes the venom components. In these animals, the last postabdominal segment, named telson, contains a pair of venomous glands connected to the stinger. The isolation of numerous scorpion toxins, along with cDNA-based gene cloning and, more recently, proteomic analyses have provided us with a large collection of venom components sequences. However, all of them are secreted, or at least are predicted to be secretable gene products. Therefore very little is known about the cellular processes that normally take place inside the glands for production of the venom mixture. To gain insights into the scorpion venom gland biology, we have decided to perform a transcriptomic analysis by constructing a cDNA library and conducting a random sequencing screening of the transcripts. Results: From the cDNA library prepared from a single venom gland of the scorpion Hadrurus gertschi, 160 expressed sequence tags (ESTs) were analyzed. These transcripts were further clustered into 68 unique sequences (20 contigs and 48 singlets), with an average length of 919 bp. Half of the ESTs can be confidentially assigned as homologues of annotated gene products. Annotation of these ESTs, with the aid of Gene Ontology terms and homology to eukaryotic orthologous groups, reveals some cellular processes important for venom gland function; including high protein synthesis, tuned posttranslational processing and trafficking. Nonetheless, the main group of the identified gene products includes ESTs similar to known scorpion toxins or other previously characterized scorpion venom components, which account for nearly 60% of the identified proteins. Conclusion: To the best of our knowledge this report contains the first transcriptome analysis of genes transcribed by the venomous gland of a scorpion. The data were obtained for the species Hadrurus gertschi, belonging to the family Caraboctonidae. One hundred and sixty ESTs were analyzed, showing enrichment in genes that encode for products similar to known venom components, but also provides the first sketch of cellular components, molecular functions, biological processes and some unique sequences of the scorpion venom gland.