CRYSTAL-STRUCTURE AT 1.1 ANGSTROM RESOLUTION OF ALPHA-CONOTOXIN PNIB - COMPARISON WITH ALPHA-CONOTOXINS PNIA AND GI

Conotoxins are small, cysteine-rich peptides isolated from the venom o f Conus spp. of predatory marine snails, which selectively target spec ific receptors and ion channels critical to the functioning of the neu romuscular system. alpha-Conotoxins PnIA and PnIB are both 16-residue peptides (differing in sequence at only two positions) isolated from t he molluscivorous snail Conus pennaceus. In contrast to the muscle-sel ective alpha-conotoxin GI from Conus geographus, PnIA and PnIB block t he neuronal nicotinic acetylcholine receptor (nAChR). Here, we describ e the crystal structure of PnIB, solved at a resolution of 1.1 Angstro m and phased using the Shake-and-Bake direct methods program. PnIB cry stals are orthorhombic and belong to the space group P2(1)2(1)2(1) wit h the following unit cell dimensions: a = 14.6 Angstrom, b = 26.1 Angs trom, and c = 29.2 Angstrom. The final refined structure of alpha-cono toxin PnIB includes all 16 residues plus 23 solvent molecules and has an overall R-factor of 14.7% (R-free of 15.9%). The crystal structures of the alpha-conotoxins PnIB and PnIA are solved from different cryst al forms, with different solvent contents. Comparison of the structure s reveals them to be very similar, showing that the unique backbone an d disulfide architecture is not strongly influenced by crystal lattice constraints or solvent interactions. This finding supports the notion that this structural scaffold is a rigid support for the presentation of important functional groups. The structures of PnIB and PnIA diffe r in their shape and surface charge distribution from that of GI.