The solution structure of frenatin 3, a neuronal nitric oxide synthase inhibitor from the giant tree frog, Litoria infrafrenata.
The peptide frenatin 3 is a major component of the skin secretion of the Australian giant tree frog, Litoria infrafrenata. Frenatin 3 is 22 amino acids in length, and shows neither antimicrobial nor anticancer activity. It inhibits the production of nitric oxide by the enzyme neuronal nitric oxide synthase at a micromolar concentration by binding to its regulatory protein, Ca2+ calmodulin, a protein known to recognize and bind amphipathic alpha-helices. The solution structure of frenatin 3 has been investigated using NMR spectroscopy and restrained molecular dynamics calculations. In trifluoroethanol/water mixtures, the peptide forms an amphipathic alpha-helix over residues 1-14 while the C-terminal eight residues are more flexible and less structured. The flexible region may be responsible for the lack of antimicrobial activity. In water, frenatin 3 exhibits some alpha-helical character in its N-terminal region.
Department of Chemistry, The University of Adelaide, South Australia, 5005, Australia.
Craig S
CS
Brinkworth
John A
JA
Carver
Kate L
KL
Wegener
Jason
J
Doyle
Lyndon E
LE
Llewellyn
John H
JH
Bowie
D000595:Amino Acid Sequence; D000818:Animals; D001001:Anura; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D012996:Solutions / Q000737:chemistry
D010455:Peptides; D012996:Solutions; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I