Solution structure of alpha-conotoxin SI.
The nuclear magnetic resonance solution structure of alpha-conotoxin SI has been determined at pH 4.2. The 36 lowest energy structures show that alpha-conotoxin SI exists in a single major solution conformation and is stabilized by six hydrogen bonds. Comparisons are made between the SI solution structure and the solution and crystal structures of alpha-conotoxin GI. Surprisingly, a high degree of similarity between the backbone conformations of the GI crystal and the SI solution structures is seen in the region of lowest sequence homology, namely residues Gly-8 to Ser-12. This similarity is more surprising when considering that in SI a proline replaces the Arg-9 found in GI. The correspondence in conformation in this region provides the definitive evidence that it is the loss of the arginine basic charge at residue 9 which determines the differences in toxicity between GI and SI, rather than any changes in conformation induced by the cyclic proline residue.
Benie
A J
AJ
Molecular and Cellular Biology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, University of London, UK.
Whitford
D
D
Hargittai
B
B
Barany
G
G
Janes
R W
RW
D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D020916:Conotoxins / Q000737:chemistry* / Q000235:genetics / Q000633:toxicity; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018733:Nicotinic Antagonists / Q000737:chemistry / Q000633:toxicity; D011487:Protein Conformation; D012996:Solutions; D013816:Thermodynamics
D020916:Conotoxins; D018733:Nicotinic Antagonists; D012996:Solutions; C057819:conotoxin SI; C029960:conotoxin GI