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Type: Journal article
Title: Investigating the importance of the flexible hinge in caerin 1.1: Solution structures and activity of two synthetically modified caerin peptides
Author: Pukala, T.
Brinkworth, C.
Carver, J.
Bowie, J.
Citation: Biochemistry, 2004; 43(4):937-944
Publisher: Amer Chemical Soc
Issue Date: 2004
ISSN: 0006-2960
Statement of
Tara L. Pukala, Craig S. Brinkworth, John A. Carver and John H. Bowie
Abstract: Caerin 1.1 is a potent broad-spectrum antibacterial peptide isolated from a number of Australian frogs of the Litoria genus. In membrane-like media, this peptide adopts two alpha-helices, separated by a flexible hinge region bounded by Pro15 and Pro19. Previous studies have suggested that the hinge region is important for effective orientation of the two helices within the bacterial cell membrane, resulting in lysis via the carpet mechanism. To evaluate the importance of the two Pro residues, they were replaced with either Ala or Gly. The antibacterial activity of these two peptides was tested, and their three-dimensional structures were determined using two-dimensional NMR spectroscopy and restrained molecular dynamics calculations. The resulting structures indicate that the central hinge angle decreases significantly upon replacement of the Pro residues with Gly and to a further extent with Ala. This trend was mirrored by a corresponding decrease in antibiotic activity, further exemplifying the necessity of the hinge in caerin 1.1 and related peptides. In a broader context, the use of Pro, Gly, and Ala variants of caerin 1.1 has enabled the relationship between conformational flexibility and activity to be directly investigated in a systematic manner.
Keywords: Animals
Antimicrobial Cationic Peptides
Amphibian Proteins
Nuclear Magnetic Resonance, Biomolecular
Microbial Sensitivity Tests
Amino Acid Substitution
Amino Acid Sequence
Protein Conformation
Protein Structure, Secondary
Structure-Activity Relationship
Hydrogen Bonding
Molecular Sequence Data
Hydrophobic and Hydrophilic Interactions
Description: Copyright © 2004 American Chemical Society
Provenance: Web Release Date: January 3, 2004
DOI: 10.1021/bi035760b
Published version:
Appears in Collections:Aurora harvest 2
Chemistry publications

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