Structural highlights
Function
[SIXP_MESMA] Excitatory insect beta-toxins induce a spastic paralysis. They bind voltage-independently at site-4 of sodium channels (Nav) and shift the voltage of activation toward more negative potentials thereby affecting sodium channel activation and promoting spontaneous and repetitive firing. This insect toxin is also active on mice, showing an analgesic effect.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
BmK IT-AP is an excitatory insect-specific beta-toxin with analgesic effect from the Chinese scorpion Buthus martensii Karsch (BmK) and consists of 72 residues cross-linked by four disulfide bridges. The crystal structure of BmK IT-AP has been determined at a resolution of 2.6 A by molecular replacement. Compared with the mammal-selective alpha-toxins consisting of 64 residues from the scorpion BmK, the general fold of IT-AP features an additional one-and-a-half turn alpha-helix at the C-terminal residues 59-65 with a shifted disulfide bridge Cys38-Cys64. The extension and 'wiggling' of the C-terminal segment led to a reshaping of the bioactive surface, including the complete destruction of the active site RC comprising the reverse turn (8-12) and C-terminal residues 58-64, the disappearance of an active surface formed by two aromatic residues Trp38 and Tyr42 and the covering of the conserved aromatic cluster Tyr5, Tyr35 and Trp47, which are all critical for the structure and function of mammal-selective alpha-toxins. Bj-xtrIT, the only other excitatory insect-specific toxin whose three-dimensional structure has been determined, is distinct from BmK IT-AP. A functionally important five-residue alpha-helix (alpha0) formed by residues 17-21 in Bj-xtrIT is deleted in BmK IT-AP and helix alpha1 is immediately connected to Cys16 through two residues Leu17 and Phe18. Accordingly, the functional surface of this region in Bj-xtrIT has also been reshaped in IT-AP, which implies subtle differences between BmK IT-AP and Bj-xtrIT in binding to the receptor, although most other critical residues for structure and function adopt almost identical conformations. The crystal structure of IT-AP also forms a sound basis for further study of the structure-function determinants of the analgesic effect.
Structure of an excitatory insect-specific toxin with an analgesic effect on mammals from the scorpion Buthus martensii Karsch.,Li C, Guan RJ, Xiang Y, Zhang Y, Wang DC Acta Crystallogr D Biol Crystallogr. 2005 Jan;61(Pt 1):14-21. Epub 2004, Dec 17. PMID:15608371[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Li C, Guan RJ, Xiang Y, Zhang Y, Wang DC. Structure of an excitatory insect-specific toxin with an analgesic effect on mammals from the scorpion Buthus martensii Karsch. Acta Crystallogr D Biol Crystallogr. 2005 Jan;61(Pt 1):14-21. Epub 2004, Dec 17. PMID:15608371 doi:10.1107/S0907444904025703
