Protein Science, Vol 3, Issue 7 1121-1124, Copyright © 1994 by Cold Spring Harbor Laboratory Press

FOR THE RECORD

Multiple conformations of the sea anemone polypeptide anthopleurin-A in solution

M. J. SCANLON and R. S. NORTON
NMR Laboratory, Biomolecular Research Institute, Parkville 3052, Australia

Anthopleurin-A (AP-A) is a member of a family of sea anemone-derived polypeptides that interact with sodium channels in a voltage-dependent manner, producing a positive inotropic effect on the mammalian heart. There has been considerable interest in this molecule as a lead compound for the development of novel therapeutic agents. Earlier attempts to define the 3-dimensional structure of AP-A were complicated by the fact that it was found to exist in 2 conformations in solution. Using (1)H- and (13)C-NMR spectroscopy, we have now shown that this conformational heterogeneity arises from cistrans isomerization about the Gly 40-Pro 41 peptide bond and that in the major form of the protein this peptide bond adopts a cis conformation. Furthermore, the increased sensitivity afforded by higher-field NMR has allowed identification of additional minor conformations of AP-A, the origin of which is presently unknown. We believe there will be many more examples of the detection by high-field NMR of previously unobserved minor conformations of proteins in solution.
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