Structure–activity relationship of an α-toxin Bs-Tx28 from scorpion ( Buthus sindicus) venom suggests a new α-toxin subfamily (original) (raw)
Archives of biochemistry …, 2006
Scorpion venoms are among the most widely known source of peptidyl neurotoxins used for callipering different ion channels, e.g., for Na + , K + , Ca + or Cl À. An a-toxin (Bs-Tx28) has been purified from the venom of scorpion Buthus sindicus, a common yellow scorpion of Sindh, Pakistan. The primary structure of Bs-Tx28 was established using a combination of MALDI-TOF-MS, LC-ESI-MS, and automated Edman degradation analysis. Bs-Tx28 consists of 65 amino acid residues (7274.3 ± 2Da), including eight cysteine residues, and shows very high sequence identity (82-94%) with other long-chain a-neurotoxins, active against receptor site-3 of mammalian (e.g., Lqq-IV and Lqh-IV from scorpions Leiurus sp.) and insect (e.g., BJa-IT and Od-1 from Buthotus judaicus and Odonthobuthus doriae, respectively) voltage-gated Na + channels. Multiple sequence alignment and phylogenetic analysis of Bs-Tx28 with other known a-and alike toxins suggests the presence of a new and separate subfamily of scorpion a-toxins. Bs-Tx28 which is weakly active in both, mammals and insects (LD 50 0.088 and 14.3 lg/g, respectively), shows strong induction of the rat afferent nerve discharge in a dose-dependent fashion (EC 50 = 0.01 lg/mL) which was completely abolished in the presence of tetrodotoxin suggesting the binding of Bs-Tx28 to the TTX-sensitive Na +-channel. Three-dimensional structural features of Bs-Tx28, established by homology modeling, were compared with other known classical a-mammal (AaH-II), a-insect (Lqh-aIT), and alike (BmK-M4) toxins and revealed subtle variations in the Nt-, Core-, and RT-CT-domains (functional domains) which constitute a ''necklace-like'' structure differing significantly in all a-toxin subfamilies. On the other hand, a high level of conservation has been observed in the conserved hydrophobic surface with the only substitution of W43 (Y43/42) and an additional hydrophobic character at position F40 (L40/A/V/G39), as compared to the other mentioned a-toxins. Despite major differences within the primary structure and activities of Bs-Tx28, it shares a common structural and functional motif (e.g., transRT-farCT) within the RT-CT domain which is characteristic of scorpion a-mammal toxins.
FEBS Letters, 2002
A short chain peptide has been isolated from the venom of a red scorpion of Indian origin, Buthus tamulus. This peptide was puri¢ed using ion exchange and reverse phase chromatography and was characterized by molecular weight determination and amino acid sequence. The primary structure analysis shows that BtITx3 is a short peptide of 35 amino acid residues having a molecular weight of 3796 Da. The toxin shows toxicity towards the Lepidopteran species of insect Helicoverpa armigera causing £accid paralysis and even death within 24 h. It shows more than 50% homology with the short insectotoxins having four disul¢de bridges, which suggests that the toxin belongs to the class of short chain toxins blocking the chloride ion channels. This sequence homology study has also helped to bring out the structure^function relationship between the various short toxins. Homology modeling done by using template structure of a known toxin indicated that this toxin consists of a similar K K/L L sca¡old, as present in other scorpion toxins. ß 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.