Structure of variant 2 scorpion toxin from Centruroides sculpturatus Ewing.
Centruroides sculpturatus Ewing variant 2 toxin (CsE-v2) is a neurotoxin isolated from the venom of a scorpion native to the Arizona desert. The structure of CsE-v2 was solved in two different crystal forms using a combination of molecular replacement and multiple isomorphous replacement techniques. Crystals of CsE-v2 display a temperature-dependent, reversible-phase transition near room temperature. At lower temperature the space group changes from P3(2)21 to P3(1)21 with an approximate doubling of the C-axis. The small-cell structure, which has one molecule per asymmetric unit, has an R factor of 0.229 at 2.8 A resolution. The large-cell structure has two molecules per asymmetric unit and was refined at 2.2 A resolution to an R factor of 0.255. CsE-v2 is a rigid, compact structure with four intrachain disulfide bonds. The structure is similar to other long-chain beta neurotoxins, and the largest differences occur in the last six residues. The high-resolution structure of CsE-v2 corrects an error in the reported C-terminal sequence; the terminal tripeptide sequence is Ser 64-Cys 65-Ser 66 rather than Ser 64-Ser 65-Cys 66. Comparison of CsE-v2 with long-chain alpha toxins reveals four insertions and one deletion, as well as additional residues at the N and C termini. Structural alignment of alpha and beta toxins suggests that the primary distinguishing feature between the two classes is the length of the loop between the second and third strands in a three-strand beta sheet. The shorter loop in alpha toxins exposes a critical lysine side chain, whereas the longer loop in beta toxins buries the corresponding basic residue (either arginine or lysine).
Cook
William J
WJ
Department of Pathology, University of Alabama at Birmingham, 35294, USA.
Zell
Alan
A
Watt
Dean D
DD
Ealick
Steven E
SE
D000595:Amino Acid Sequence; D000818:Animals; D001130:Arizona; D018360:Crystallography, X-Ray; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012604:Scorpion Venoms / Q000737:chemistry*; D012605:Scorpions / Q000737:chemistry*
D012604:Scorpion Venoms; C043052:variant-2 scorpion toxin