Toxin II From The Scorpion Androctonus Australis Hector
a supplement to BCM496H: Lab 2
The structure of scorpion toxin II, isolated from the scorpion Androctonus Australis Hector, was determined by D.Housset, C.Habersetzer-Rochat, J.-P.Astier, and J.C.Fontecilla-Camps using X-ray diffraction.(1) According to the Structural Classification of Proteins databank (SCOP), the toxin is classified as a small protein, dominated by disulfide bridges, with a knottin fold, " a disulfide-bound fold and a beta-hairpin with two adjacent disulfides." (2) The primary structure of the molecule is made up of sixty-four residues.
According to the author's secondary structure determination, the molecule contains
one alpha helix and three beta sheets. The alpha helix (magenta structure at
right) begins at asn19 and ends at lys28. The first beta sheet (yellow structure
at right)starts at the
second residue, lysine, and stops at the fourth residue, glycine. Residues
glu32 to gln37 make up the second beta sheet. The third, and longest, sheet is
composed of amino acids ala45 through leu51.
Kabsch and Sander's DSSP algorithm identified secondary structure not reported
by the authors. In addition to the alpha helix and three beta sheets above,
the DSSP calculation found six beta sheets and ten turns. All of the six are made
up of only a single amino acid, and so would probably not be considered true
beta sheets. These six sheets were made up of the following residues; lys2, thr13,
ser40, gly43, leu51, and thr57. Ten turns were reported by the algorithm at asp9-asn11,
gly17, leu29-lys30, glu32, trp38-ala39, pro41-tyr42, asn44, lys50, asp53-val55, and
pro60-gly61.
The Androctonus genus of scorpion produces a very toxic venom that may induce "malignant hypothermia, myocarditis, pulmonary edema," or even death. All of the "important" residues appear to be grouped on one side of the toxin, indicating that "this solvent-exposed hydrophobic surface" is the point of interaction and that "adjacent areas modulate the specificity of the interaction." The toxicity, therefore, lies in the residues that make up this conserved hydrophobic surface as well as the C- and N-terminals.(3) According to an article in the European Journal of Biochemistry in 1989, tryptophan 38 in scorpion toxin II was replaced with nitrophenylsulfenyl chloride, resulting in a less active substance.(4) This would seem to support that the conserved surface controls the reactivity of the toxin.
References
(1) http://www.pdb.bnl.gov/pdb-bin/pdbids?id=1ptx
(2) http://pdb.pdb.bnl.gov/scop/data/scop.1.007.003.006.001.004.html
(3) http://cobras.org/wwwboard/_discuss2/00000029.htm
(4) http://afmb.cnrs-mrs.fr/subjects/a-sctx2.html
Jacqueline Campbell University of Georgia August 5, 1998