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https://hdl.handle.net/2440/17958
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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 1520-4995 |
Statement of Responsibility: | 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 Anura Bacteria Alanine Proline Glycine Antimicrobial Cationic Peptides Amphibian Proteins Solutions Nuclear Magnetic Resonance, Biomolecular Microbial Sensitivity Tests Amino Acid Substitution Amino Acid Sequence Protein Conformation Protein Structure, Secondary Structure-Activity Relationship Hydrogen Bonding Thermodynamics 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: | http://pubs.acs.org/cgi-bin/abstract.cgi/bichaw/2004/43/i04/abs/bi035760b.html |
Appears in Collections: | Aurora harvest 2 Chemistry publications |
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