THE 1.2 Å STRUCTURE OF G1, AN [[alpha]]-CONOTOXIN PEPTIDE. L. W. Guddat^*, L. Shan#, J. L. Martin^*, A. B. Edmundson^#, W. R. Gray[[section]]* Centre for Drug Design & Development, U. Queensland, Brisbane 4072, QLD^, Australia. #Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK, USA^, [[section]]201 So. Biology, University of Utah, Salt Lake City, UT 84112,

The crystal structure of a synthetic thirteen residue peptide that represents [[alpha]]-conotoxin G1 from marine snail Conus Geographus has been determined to 1.2 Å resolution. Structural studies of G1 are of particular interest because it is known to block synaptic transmission by binding to the acetylcholine receptor. This structure, which contains 117 atoms, was solved by direct methods implementing the program SHAKE-AND-BAKE[1]. The framework of the toxin includes two disulphide bonds that link residues 2-7 and 3-13. The side chain of the amino terminal residue and the amide from the carboxy terminus form a hydrogen bond, making the peptide in the shape of a closed loop. The two termini are further drawn together by additional main chain hydrogen bonds. The two positively charged regions, the amino terminus and the guanidinium group of arg-9 are separated by 15 Å, a value consistent with other acetylcholine agonists such as curare[2,3]. The X-ray structure of G1 will be compared with structures derived by NMR and a predictive model based on a CD spectrum[4-6].

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