Identification of structural traits that increase the antimicrobial activity of a chimeric peptide of human beta-defensins 2 and 3

Spudy, B., Sönnichsen, F. D., Wätzig, G. H., Grötzinger, J. and Jung, S. (2012) Identification of structural traits that increase the antimicrobial activity of a chimeric peptide of human beta-defensins 2 and 3 Biochemical and Biophysical Research Communications, 427 (1). pp. 207-211.

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Abstract

Antimicrobial peptides participate in the first line of defence of many organisms against pathogens. In humans, the family of beta-defensins plays a pivotal role in innate immunity. Two human beta-defensins, beta-defensin-2 and -3 (HBD2 and HBD3), show substantial sequence identity and structural similarity. However, HBD3 kills Staphylococcus (S.) aureus with a 4- to 8-fold higher efficiency compared to HBD2, whereas their activities against Escherichia (E.) coil are very similar. The generation of six HBD2/HBD3-chimeric molecules led to the identification of distinct molecular regions which mediate their divergent killing properties. One of the chimeras (chimera C3) killed both E. coil and S. aureus with an even higher efficacy compared to the wild-type molecules. Due to the broad spectrum of its antimicrobial activity against many human multidrug-resistant pathogens, this HBD2/HBD3-chimeric peptide represents a promising candidate for a new class of antibiotics. In order to investigate the structural basis of its exceptional antimicrobial activity, the peptide's tertiary structure was determined by NMR spectroscopy, which allowed its direct comparison to the published structures of HBD2 and HBD3 and the identification of the activity-increasing molecular features. (C) 2012 Elsevier Inc. All rights reserved.

Document Type: Article
Additional Information: Univ Kiel, Inst Biochem, D-24098 Kiel, Germany. Univ Kiel, Otto Diels Inst Organ Chem, D-24098 Kiel, Germany. CONARIS Res Inst AG, D-24118 Kiel, Germany. Grotzinger, J (reprint author), Univ Kiel, Inst Biochem, Olshausenstr 40, D-24118 Kiel, Germany. jgroetzinger@biochem.uni-kiel.de
Keywords: Human beta-defensin Structure Antimicrobial peptide Antimicrobial activity NMR human beta-defensin-2 macromolecular structures innate immunity cytotoxicity program design system alpha
Research affiliation: OceanRep > The Future Ocean - Cluster of Excellence
ISSN: 0006-291X
Projects: Future Ocean
Date Deposited: 14 May 2014 09:16
Last Modified: 14 May 2014 09:16
URI: http://eprints.uni-kiel.de/id/eprint/24265

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