Solution Structure of Contryphan-R, a Naturally Occurring Disulfide-Bridged Octapeptide Containing d-Tryptophan:  Comparison with Protein Loops

• Published in: Biochemistry (Easton) 1999-08, Vol.38 (35), p.11553-11559
• Main Authors: Pallaghy, Paul K, Melnikova, Albina P, Jimenez, Elsie C, Olivera, Baldomero M, Norton, Raymond S
• Format: Article
• Language: English
• Subjects: Animals; Crystallography, X-Ray; Disulfides - chemistry; Hydrogen Bonding; Models, Molecular; Mollusk Venoms - chemistry; Nuclear Magnetic Resonance, Biomolecular; Oligopeptides - chemistry; Peptide Fragments - chemistry; Peptides, Cyclic - chemistry; Protein Conformation; Protein Folding; Solutions; Tryptophan - chemistry
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi990685j

Contryphan-R is a disulfide-constrained octapeptide containing a d-tryptophan 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 isomerization at hydroxyproline 3. The solution structure of the major form of this unusual polypeptide, determined from NMR data, consists of a well-defined fold containing a non-hydrogen-bonded chain reversal from Gly1 to Glu5, which includes a cis-hydroxyproline and a d-Trp, and a type I β-turn from Glu5 to Cys8. The presence of a putative salt bridge between the Glu5 carboxyl group and the N-terminal ammonium group is investigated by using various solvation models during energy minimization and is compared with the results of a pH titration. A comparison of the structure of contryphan-R with other cyclic peptide structures highlights some of the key structural determinants of these peptides and suggests that the contryphan-R fold could be exploited 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 found in proteins.