Cargando…

Discovery and Characterization of a Disulfide-Locked C(2)-Symmetric Defensin Peptide

[Image: see text] We report the discovery of HD5-CD, an unprecedented C(2)-symmetric β-barrel-like covalent dimer of the cysteine-rich host-defense peptide human defensin 5 (HD5). Dimerization results from intermonomer disulfide exchange between the canonical α-defensin Cys(II)–Cys(IV) (Cys(5)–Cys(2...

Descripción completa

Detalles Bibliográficos
Autores principales: Wommack, Andrew J., Ziarek, Joshua J., Tomaras, Jill, Chileveru, Haritha R., Zhang, Yunfei, Wagner, Gerhard, Nolan, Elizabeth M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183617/
https://www.ncbi.nlm.nih.gov/pubmed/25181039
http://dx.doi.org/10.1021/ja505957w
_version_ 1782337726833491968
author Wommack, Andrew J.
Ziarek, Joshua J.
Tomaras, Jill
Chileveru, Haritha R.
Zhang, Yunfei
Wagner, Gerhard
Nolan, Elizabeth M.
author_facet Wommack, Andrew J.
Ziarek, Joshua J.
Tomaras, Jill
Chileveru, Haritha R.
Zhang, Yunfei
Wagner, Gerhard
Nolan, Elizabeth M.
author_sort Wommack, Andrew J.
collection PubMed
description [Image: see text] We report the discovery of HD5-CD, an unprecedented C(2)-symmetric β-barrel-like covalent dimer of the cysteine-rich host-defense peptide human defensin 5 (HD5). Dimerization results from intermonomer disulfide exchange between the canonical α-defensin Cys(II)–Cys(IV) (Cys(5)–Cys(20)) bonds located at the hydrophobic interface. This disulfide-locked dimeric assembly provides a new element of structural diversity for cysteine-rich peptides as well as increased protease resistance, broad-spectrum antimicrobial activity, and enhanced potency against the opportunistic human pathogen Acinetobacter baumannii.
format Online
Article
Text
id pubmed-4183617
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-41836172015-09-02 Discovery and Characterization of a Disulfide-Locked C(2)-Symmetric Defensin Peptide Wommack, Andrew J. Ziarek, Joshua J. Tomaras, Jill Chileveru, Haritha R. Zhang, Yunfei Wagner, Gerhard Nolan, Elizabeth M. J Am Chem Soc [Image: see text] We report the discovery of HD5-CD, an unprecedented C(2)-symmetric β-barrel-like covalent dimer of the cysteine-rich host-defense peptide human defensin 5 (HD5). Dimerization results from intermonomer disulfide exchange between the canonical α-defensin Cys(II)–Cys(IV) (Cys(5)–Cys(20)) bonds located at the hydrophobic interface. This disulfide-locked dimeric assembly provides a new element of structural diversity for cysteine-rich peptides as well as increased protease resistance, broad-spectrum antimicrobial activity, and enhanced potency against the opportunistic human pathogen Acinetobacter baumannii. American Chemical Society 2014-09-02 2014-10-01 /pmc/articles/PMC4183617/ /pubmed/25181039 http://dx.doi.org/10.1021/ja505957w Text en Copyright © 2014 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html)
spellingShingle Wommack, Andrew J.
Ziarek, Joshua J.
Tomaras, Jill
Chileveru, Haritha R.
Zhang, Yunfei
Wagner, Gerhard
Nolan, Elizabeth M.
Discovery and Characterization of a Disulfide-Locked C(2)-Symmetric Defensin Peptide
title Discovery and Characterization of a Disulfide-Locked C(2)-Symmetric Defensin Peptide
title_full Discovery and Characterization of a Disulfide-Locked C(2)-Symmetric Defensin Peptide
title_fullStr Discovery and Characterization of a Disulfide-Locked C(2)-Symmetric Defensin Peptide
title_full_unstemmed Discovery and Characterization of a Disulfide-Locked C(2)-Symmetric Defensin Peptide
title_short Discovery and Characterization of a Disulfide-Locked C(2)-Symmetric Defensin Peptide
title_sort discovery and characterization of a disulfide-locked c(2)-symmetric defensin peptide
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183617/
https://www.ncbi.nlm.nih.gov/pubmed/25181039
http://dx.doi.org/10.1021/ja505957w
work_keys_str_mv AT wommackandrewj discoveryandcharacterizationofadisulfidelockedc2symmetricdefensinpeptide
AT ziarekjoshuaj discoveryandcharacterizationofadisulfidelockedc2symmetricdefensinpeptide
AT tomarasjill discoveryandcharacterizationofadisulfidelockedc2symmetricdefensinpeptide
AT chileveruharithar discoveryandcharacterizationofadisulfidelockedc2symmetricdefensinpeptide
AT zhangyunfei discoveryandcharacterizationofadisulfidelockedc2symmetricdefensinpeptide
AT wagnergerhard discoveryandcharacterizationofadisulfidelockedc2symmetricdefensinpeptide
AT nolanelizabethm discoveryandcharacterizationofadisulfidelockedc2symmetricdefensinpeptide