1I6G

NMR SOLUTION STRUCTURE OF THE INSECT-SPECIFIC NEUROTOXIN VARIANT 5 (CSE-V5) FROM THE SCORPION CENTRUROIDES SCULPTURATUS EWING

Summary for 1I6G

• Entry DOI: 10.2210/pdb1i6g/pdb
• Related: 1B3C 1IGF 1NRB
• Descriptor: NEUROTOXIN V-5 (1 entity in total)
• Functional Keywords: scorpion, neurotoxin, sodium channel, alpha helix, beta sheet, disulfide linkages, toxin
• Biological source: Centruroides sculpturatus (bark scorpion)
• Total number of polymer chains: 1
• Total formula weight: 6370.23

Authors

Jablonsky, M.J.,Jackson, P.L.,Krishna, N.R. (deposition date: 2001-03-02, release date: 2001-08-01, Last modification date: 2024-10-16)

Primary citation

Jablonsky, M.J.,Jackson, P.L.,Krishna, N.R.
Solution structure of an insect-specific neurotoxin from the New World scorpion Centruroides sculpturatus Ewing.
Biochemistry, 40:8273-8282, 2001

PubMed Abstract: We report the high-resolution solution structure of the 6.3 kDa neurotoxic protein CsE-v5 from the scorpion Centruroides sculpturatus Ewing (CsE, range southwestern U.S.). This protein is the second example of an Old World-like neurotoxin isolated from the venom of this New World scorpion. However, unlike CsE-V, which is the first Old World-like toxin isolated and shows both anti-insect and anti-mammal activity, CsE-v5 shows high specificity for insect sodium channels. Sequence-specific proton NMR assignments and distance and angle constraints were obtained from 600 MHz 2D-NMR data. Distance geometry and dynamical simulated annealing refinements were performed to produce a final family of 20 structures without constraint violations, along with an energy-minimized average structure. The protein structure is well-defined (0.66 and 0.97 D rmsd for backbone and all heavy atoms, respectively) with a compact hydrophobic core and several extending loops. A large hydrophobic patch, containing four aromatic rings and other aliphatic residues, makes up a large area of one side of the protein. CsE-v5 shows secondary structural features characteristic of long-chain scorpion toxins: a two and a half-turn alpha-helix, a three-strand antiparallel beta-sheet, and four beta-turns. Among the proteins studied to date from the CsE venom, CsE-v5 is the most compact protein with nearly 50% of the amide protons having long exchange lifetimes, but CsE-v5 is unusual in that it has loop structures similar to both Old and New World toxins. Further, it also lacks prolines in its C-terminal 14 residues. It shows some important differences with respect to CsE-V not only in its primary sequence, but also in its electrostatic potential surface, especially around areas in register with residues 8, 9, 17, 18, 32, 43, and 57. The loss of anti-mammal activity in CsE-v5 and the differences in its anti-insect activity compared to that of other proteins such as CsE-V, v1, and v3 from this New World scorpion may be related to residue variations at these locations.

PubMed: 11444973
DOI: 10.1021/bi010223h

Experimental method

SOLUTION NMR