Detailed assessment of spatial hydrophobic and electrostatic properties of 2D NMR-derived models of neurotoxin II.

2D NMR-derived spatial structures of neurotoxin II (NtII) and several homologous toxins in solution were assessed by comparison with their own amino acid sequences using a three-dimensional (3D) profile method. 3D profiles of all the toxin models match the sequences well and, therefore, the method of 3D profile was demonstrated to work correctly for these well-resolved NMR structures in aqueous solution. At the same time, the profile window plots reveal low scores in the bottom tip of loop II (residues 22-34 in NtII) and in beta-strand of loop III (residues 49-52). Some residues in the first poor-scoring region are of functional importance being involved in binding with nicotinic acetylcholine receptor (AChR). Furthermore, the second segment participates in intermolecular hydrogen bonding upon dimerization of postsynaptic neurotoxins in solution resulting in increasing of the 3D-1D score for residues at the interface between monomers. Therefore, the 3D profile method can be useful for detection functionally-important regions in well-resolved protein structures.