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

Open Access
Publisher Website
Google Scholar
Abstract
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. Using1H‐ and13C‐NMR spectroscopy, we have now shown that this conformational heterogeneity arises fromcis–transisomerization about the Gly 40–Pro 41 peptide bond and that in the major form of the protein this peptide bond adopts acisconformation. 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.