1T0Z

Structure of an Excitatory Insect-specific Toxin with an Analgesic Effect on Mammalian from Scorpion Buthus martensii Karsch

Summary for 1T0Z

• Entry DOI: 10.2210/pdb1t0z/pdb
• Descriptor: insect neurotoxin, SULFATE ION (3 entities in total)
• Functional Keywords: alpha-beta, toxin
• Biological source: Mesobuthus martensii (Chinese scorpion)
• Cellular location: Secreted: O77091
• Total number of polymer chains: 2
• Total formula weight: 17387.23

Authors

Li, C.,Guan, R.-J.,Xiang, Y.,Zhang, Y.,Wang, D.-C. (deposition date: 2004-04-14, release date: 2004-12-28, Last modification date: 2024-10-30)

Primary citation

Li, C.,Guan, R.J.,Xiang, Y.,Zhang, Y.,Wang, D.C.
Structure of an excitatory insect-specific toxin with an analgesic effect on mammals from the scorpion Buthus martensii Karsch.
Acta Crystallogr.,Sect.D, 61:14-21, 2005

PubMed Abstract: 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.

PubMed: 15608371
DOI: 10.1107/S0907444904025703

Experimental method

X-RAY DIFFRACTION (2.6 Å)