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-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 beta-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.
Pallaghy
P K
PK
Biomolecular Research Institute, Parkville, Australia.
Melnikova
A P
AP
Jimenez
E C
EC
Olivera
B M
BM
Norton
R S
RS
D000818:Animals; D018360:Crystallography, X-Ray; D004220:Disulfides / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008978:Mollusk Venoms / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D011487:Protein Conformation; D017510:Protein Folding; D012996:Solutions; D014364:Tryptophan / Q000737:chemistry*
D004220:Disulfides; D008978:Mollusk Venoms; D009842:Oligopeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D012996:Solutions; C102355:contryphan; D014364:Tryptophan