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Investigating the importance of the flexible hinge in caerin 1.1: Solution structures and activity of two synthetically modified caerin peptides

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dc.contributor.authorPukala, T.
dc.contributor.authorBrinkworth, C.
dc.contributor.authorCarver, J.
dc.contributor.authorBowie, J.
dc.date.issued2004
dc.descriptionCopyright © 2004 American Chemical Society
dc.description.abstractCaerin 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.
dc.description.statementofresponsibilityTara L. Pukala, Craig S. Brinkworth, John A. Carver and John H. Bowie
dc.identifier.citationBiochemistry, 2004; 43(4):937-944
dc.identifier.doi10.1021/bi035760b
dc.identifier.issn0006-2960
dc.identifier.issn1520-4995
dc.identifier.orcidPukala, T. [0000-0001-7391-1436]
dc.identifier.urihttp://hdl.handle.net/2440/17958
dc.language.isoen
dc.provenanceWeb Release Date: January 3, 2004
dc.publisherAmer Chemical Soc
dc.source.urihttp://pubs.acs.org/cgi-bin/abstract.cgi/bichaw/2004/43/i04/abs/bi035760b.html
dc.subjectAnimals
dc.subjectAnura
dc.subjectBacteria
dc.subjectAlanine
dc.subjectProline
dc.subjectGlycine
dc.subjectAntimicrobial Cationic Peptides
dc.subjectAmphibian Proteins
dc.subjectSolutions
dc.subjectNuclear Magnetic Resonance, Biomolecular
dc.subjectMicrobial Sensitivity Tests
dc.subjectAmino Acid Substitution
dc.subjectAmino Acid Sequence
dc.subjectProtein Conformation
dc.subjectProtein Structure, Secondary
dc.subjectStructure-Activity Relationship
dc.subjectHydrogen Bonding
dc.subjectThermodynamics
dc.subjectMolecular Sequence Data
dc.subjectHydrophobic and Hydrophilic Interactions
dc.titleInvestigating the importance of the flexible hinge in caerin 1.1: Solution structures and activity of two synthetically modified caerin peptides
dc.typeJournal article
pubs.publication-statusPublished

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