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.
Molecular and Cellular Biology, St. Bartholomew's and the Royal London School of Medicine and Dentistry, University of London, UK.
A J
AJ
Benie
D
D
Whitford
B
B
Hargittai
G
G
Barany
R W
RW
Janes
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