STRUCTURE OF FASCICULIN-2 FROM GREEN MAMBA SNAKE-VENOM - EVIDENCE FORUNUSUAL LOOP FLEXIBILITY

The crystal structure of the snake toxin fasciculin 2, a potent acetyl cholinesterase inhibitor from the venom of the green mamba (Dendroaspi s angusticeps), has been determined by the molecular-replacement metho d, using the fasciculin 1 model and refined to 2.0 Angstrom resolution . The introduction of an overall anisotropic temperature factor improv ed significantly the quality of the electron-density map. It suggests, as it was also indicated by the packing, that the thermal motion alon g the unique axis direction is less pronounced than on the (ab) plane. The final crystallographic R factor is 0.188 for a model having r.m.s . deviations from ideality of 0.016 Angstrom for bond lengths and 2.01 degrees for bond angles. As fasciculin 1, fasciculin 2 belongs to the three-finger class of Elapidae toxins, a structural group that also c ontains the alpha neurotoxins and the cardiotoxins. Although the two f asciculins have, overall, closely related structures, the conformation of loop I differs appreciably in the two molecules. The presence of d etergent in crystallization medium in the case of fasciculin 2 appears to be responsible for the displacement of the loop containing Thr9. T his conformational change also results in the formation of a crystallo graphic dimer that displays extensive intermolecular interactions.