Impact of single-residue mutations on the structure and function of ovispirin/novispirin antimicrobial peptides

Monali V Sawai; Alan J Waring; William R Kearney; Paul B McCray; William R Forsyth; Robert I Lehrer; Brian F Tack

doi:10.1093/protein/15.3.225

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Impact of single-residue mutations on the structure and function of ovispirin/novispirin antimicrobial peptides

Journal article

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Impact of single-residue mutations on the structure and function of ovispirin/novispirin antimicrobial peptides

Monali V Sawai, Alan J Waring, William R Kearney, Paul B McCray, William R Forsyth, Robert I Lehrer and Brian F Tack

Protein engineering, Vol.15(3), pp.225-232

03/2002

DOI: 10.1093/protein/15.3.225

PMID: 11932493

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Abstract

We studied three model antibacterial peptides that resembled the N-terminal 18 amino acids of SMAP-29, an α-helical, antimicrobial peptide of sheep. Although the parent compound, ovispirin-1 (KNLRR IIRKI IHIIK KYG), was potently antimicrobial, it was also highly cytotoxic to human epithelial cells and hemolytic for human erythrocytes. Single residue substitutions to ovispirin-1 yielded two substantially less cytotoxic peptides (novispirins), with intact antimicrobial properties. One of these, novispirin G-10, differed from ovispirin-1 only by containing glycine at position 10, instead of isoleucine. The other, novispirin T-7, contained threonine instead of isoleucine at position 7. We determined the three-dimensional solution structures of all three peptides by circular dichroism spectroscopy and two-dimensional nuclear magnetic resonance spectroscopy. Although all retained an amphipathic helical structure in 2,2,2-trifluoroethanol, they manifested subtle fine-structural changes that evidently impacted their activities greatly. These findings show that simple structural modifications can `fine-tune' an antimicrobial peptide to minimize unwanted cytotoxicity while retaining its desired activity.

solution structure

NMR

amphipathic

antimicrobial peptides

Details

Title: Subtitle: Impact of single-residue mutations on the structure and function of ovispirin/novispirin antimicrobial peptides
Creators: Monali V Sawai - Department of Microbiology
Alan J Waring - Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90095 and
William R Kearney - NMR Facility and
Paul B McCray - Department of Pediatrics, University of Iowa College of Medicine, Iowa City, IA 52242
William R Forsyth - Department of Chemistry and Center for Biomolecular Structure and Function, Pennsylvania State University, University Park, PA 16802, USA
Robert I Lehrer - Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90095 and
Brian F Tack - Department of Microbiology
Resource Type: Journal article
Publication Details: Protein engineering, Vol.15(3), pp.225-232
DOI: 10.1093/protein/15.3.225
PMID: 11932493
NLM abbreviation: Protein Eng
ISSN: 0269-2139
eISSN: 1460-213X
Publisher: Oxford University Press
Language: English
Date published: 03/2002
Academic Unit: Radiology; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
Record Identifier: 9984093468902771

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