The toxin pictured above was isolated by V.Tugarinov, I.Kustanovich, N.Zilberberg, M.Gurevitz, and J.Anglister from the scorpion Leiurus quinquestriatus hebraeus (1). According to the 3DB Atlas databank, this compound is classified as insect toxin alpha under the class neurotoxin (2). According to the Structural Classification of Proteins databank, the molecule is a small protein "usually dominated by metal ligand, heme, and/or disulfide bridges." This toxin is dominated by disulfide bridges (shown at right in yellow). The fold of the molecule is a knottin, a small toxin defined to have "a disulfide-bound fold and a beta-hairpin with two adjacent disulfides" (3). The structure is made up of an amino acid chain containing sixty-four residues.

According to the authors' structure determination, the toxin has one alpha helix (shown at left in magenta) and two beta sheets (shown at left in yellow) (1). The alpha helix starts at the twentieth residue, aspartate,and terminates with asparagine in the thirtieth position. The first beta sheet begins with ser34 and ends with gln38. Ala46 through tyr50 make up the second beta sheet.

Kabsch and Sander's DSSP algorithm identified secondary structure not reported by the authors. In addition to the alpha helix and two beta sheets above, the DSSP calculation found four beta sheets. Three of the four were made up of only a single amino acid (arg3, leu52, and leu58) and so would probably not be considered beta sheets though they might demonstrate some qualities of beta sheets (hydrogen bonding, "puckering"). The fourth beta sheet found by DSSP was made up of three amino acids beginning with ala5 and ending with leu7. Though short, one might argue that this segment is a legitimate beta sheet. The algorithm also designated eight turns (shown at right in blue) as secondary structure (asp8 through asn12; phe18 through arg19; gly31; ser33; ala40 through asn45; ala51; asp54 through val56; and pro61 through gly62).

The scorpion Leiurus quinquestriatus hebraeus carries a number of very potent neurotoxins which act to block sodium and potassium channels in the body (4). While this action is the key to the mechanism of the poison, pharmaceutical companies have expressed interest in how the toxin might be used in medicine. Because these channels have been linked to the regulation of insulin in the body, there may be some use of this toxin to treat diabetics. The toxin appears to lend itself to applications other than its natural function. Claudio Vita and colleagues in France have taken advantage of the physical structure of the toxin to engineer molecules with "different biological properties," essentially using the stability of the folding structure to build other molecules (4).

(1) http://www.embl-heidelberg.de/srs5bin/cgi-bin/wgetz?-e+[PDB-ID:1lqh]

(2) http://bcl10.bmb.uga.edu/pdb-bin/pdbids

*Search for 1LQH in the Protein Databank Browser

(3) http://wehih.wehi.edu.au/scop/data/scop.1.007.003.006.html

(4) http://ci.mond.org/9522/952214.html

Jacqueline Campbell      University of Georgia      July 17,1998