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The solution structure of frenatin 3, a neuronal nitric oxide synthase inhibitor from the giant tree frog, Litoria infrafrenata
Author(s) -
Brinkworth Craig S.,
Carver John A.,
Wegener Kate L.,
Doyle Jason,
Llewellyn Lyndon E.,
Bowie John H.
Publication year - 2003
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.10524
Subject(s) - chemistry , peptide , nitric oxide synthase , nitric oxide , tree frog , calmodulin , stereochemistry , amphiphile , frog skin , helix (gastropod) , enzyme , sponge , biochemistry , biophysics , organic chemistry , copolymer , botany , biology , polymer , ecology , sodium , snail
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