Solution Structure of Toxin b, a Long Neurotoxin from the Venom of the King Cobra (Ophiophagus hannah)

Shi-Shung Peng,Thallampuranam Krishnaswamy S Kumar,Gurunathan Jayaraman,Chun-Chang Chang,Chin Yu

doi:10.1074/jbc.272.12.7817

Shi-Shung Peng, Thallampuranam Krishnaswamy S Kumar + Show 3 more

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https://doi.org/10.1074/jbc.272.12.7817

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Abstract

The solution structure of toxin b, a long neurotoxin (73 amino acids and 5 disulfides) from the venom of Ophiophagus hannah (king cobra), has been determined using 1H NMR and dynamical simulated annealing techniques. The structures were calculated using 485 distance constraints and 52 dihedral angle restraints. The 21 structures that were obtained satisfy the experimental restraints and possess good nonbonded contacts. Analysis of the converged structures revealed that the protein consists of a core region from which three finger-like loops extend outwards. The regular secondary structure in toxin b includes a double and a triple stranded antiparallel beta sheet. Comparison with the solution structures of other long neurotoxins reveals that although the structure of toxin b is similar to those of previously reported long neurotoxins, clear local structural differences are observed in regions proposed to be involved in binding to the acetylcholine receptor. A positively charged cluster is found in the C-terminal tail, in Loop III, and in the tip of Loop II. This cationic cluster could be crucial for the binding of the long neurotoxins to the acetylcholine receptor.

Highlights

Deletion within the main chain itself, long neurotoxins have an extra polypeptide chain between residues 65 and 73 that gives rise to a characteristic C-terminal tail [2]
We find that the overall fold of toxin b is similar to that of the other long neurotoxin structures
Structure Description—The three-dimensional structure of toxin b consists of three hairpin-type loops emerging from a globular head

Summary

Introduction

Deletion within the main chain itself, long neurotoxins have an extra polypeptide chain between residues 65 and 73 that gives rise to a characteristic C-terminal tail [2]. Venom of snakes from the Elapidae and Hydrophyidae families possesses proteins with pronounced pharmacological activities [1, 2]. Some of these proteins are potent cardiotoxins [3, 4], whereas others are postsynaptic neurotoxins [5,6,7]. The neurotoxins are classified into two general groups, long and short neurotoxins [8, 9] Both classes of toxins bind to the nicotinic acetylcholine receptor and block synaptic nerve transmission [10, 11]. The atomic coordinates and structure factors (codes 1TXA and 1TXB) have been deposited in the Protein Data Bank, Brookhaven National Laboratory, Upton, NY

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Conclusion