The refined crystal structure of alpha-cobratoxin from Naja naja siamensis at 2.4-A resolution.

Abstract

The crystal structure of the "long" a-neurotoxin acobratoxin was refined to an R-factor of 19.5% using 3271 x-ray data to 2.4-A resolution.The polypeptide chain forms three loops, I, 11,111, knotted together by four disulfide bridges, with the most prominent, loop 11, containing another disulfide close to its lower tip.Loop I is stabilized by one @-turn and two &sheet hydrogen bonds; loop I1 by eight @-sheet hydrogen bonds, with the tip folded into two distorted righthanded helical turns stabilized by two a-helical and two &turn hydrogen bonds; and loop I11 by hydrophobic interactions and one &turn.Loop I1 and one strand of loop I11 form an antiparallel triple-pleated &sheet, and tight anchoring of the Asns3 side chain fixes the tail segment.In the crystal lattice, the a-cobratoxin molecules dimerize by &sheet formation between strands 63 and 57 of symmetry-related molecules.Because such interactions are found also in a cardiotoxin and a-bungarotoxin, this could be of importance for interaction with acetylcholine receptor.