The solution structure of frenatin 3, a neuronal nitric oxide synthase inhibitor from the giant tree frog, Litoria infrafrenata

✍ Scribed by Craig S. Brinkworth; John A. Carver; Kate L. Wegener; Jason Doyle; Lyndon E. Llewellyn; John H. Bowie

• Publisher: Wiley (John Wiley & Sons)
• Year: 2003
• Tongue: English
• Weight: 357 KB
• Volume: 70
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.10524

✦ Synopsis

Abstract

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, Ca^2+^ calmodulin, a protein known to recognize and bind amphipathic α‐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 α‐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 α‐helical character in its N‐terminal region. © 2003 Wiley Periodicals, Inc. Biopolymers 70: 424–434, 2003