Solution structure of contryphan-R, a naturally occurring disulfide-bridged octapeptide containing D-tryptophan: Comparison with protein loops

Contryphan-R is a disulfide-constrained octapeptide containing a D-tryptoph an that was isolated recently from venom of the cone shell Conus radiatus. The polypeptide is present in two forms in solution due to cis-trans isomer ization at hydroxyproline 3, The solution structure of the major form of th is unusual polypeptide, determined from NMR data, consists of a well-define d fold containing a non-hydrogen-bonded chain reversal from Gly1 to Glu5, w hich includes a cis-hydroxyproline and a D-Trp, and a type I P-turn from Gl u5 to Cys8. The presence of a putative salt bridge between the Glu5 carboxy l group and the N-terminal ammonium group is investigated by using various solvation models during energy minimization and is compared with the result s of a pH titration. A comparison of the structure of contryphan-R with oth er cyclic peptide structures highlights some of the key structural determin ants of these peptides and suggests that the contryphan-R fold could be exp loited as a scaffold onto which unrelated protein binding surfaces could be grafted, Comparison with small disulfide-bridged loops in larger proteins shows that contryphan-R is similar to a commonly occurring loop structure f ound in proteins.