The refined crystal structure of alpha-cobratoxin from Naja naja siamensis at 2.4-A resolution.
The crystal structure of the "long" alpha-neurotoxin alpha-cobratoxin 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, II, III, knotted together by four disulfide bridges, with the most prominent, loop II, containing another disulfide close to its lower tip. Loop I is stabilized by one beta-turn and two beta-sheet hydrogen bonds; loop II by eight beta-sheet hydrogen bonds, with the tip folded into two distorted right-handed helical turns stabilized by two alpha-helical and two beta-turn hydrogen bonds; and loop III by hydrophobic interactions and one beta-turn. Loop II and one strand of loop III form an antiparallel triple-pleated beta-sheet, and tight anchoring of the Asn63 side chain fixes the tail segment. In the crystal lattice, the alpha-cobratoxin molecules dimerize by beta-sheet formation between strands 53 and 57 of symmetry-related molecules. Because such interactions are found also in a cardiotoxin and alpha-bungarotoxin, this could be of importance for interaction with acetylcholine receptor.
European Molecular Biology Laboratory, Deutsches Elektronen Synchrotron, Hamburg, Federal Republic of Germany.
C
C
Betzel
G
G
Lange
G P
GP
Pal
K S
KS
Wilson
A
A
Maelicke
W
W
Saenger
D000595:Amino Acid Sequence; D000818:Animals; D003039:Cobra Neurotoxin Proteins / Q000737:chemistry* / Q000302:isolation & purification; D003545:Cysteine; D004220:Disulfides / Q000032:analysis; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011487:Protein Conformation; D012911:Snakes; D012997:Solvents; D014961:X-Ray Diffraction / Q000379:methods
D003039:Cobra Neurotoxin Proteins; D004220:Disulfides; D012997:Solvents; C025154:alpha-cobratoxin; D003545:Cysteine