Discovery and Characterization of a Disulfide-Locked C[subscript 2]-Symmetric Defensin Peptide
We report the discovery of HD5-CD, an unprecedented C[subscript 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[superscript II]–Cys[superscript I...
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| Format: | Article |
| Language: | en_US |
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American Chemical Society
2017
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| Online Access: | http://hdl.handle.net/1721.1/109106 https://orcid.org/0000-0002-2515-5901 https://orcid.org/0000-0002-6426-2291 https://orcid.org/0000-0002-6153-8803 |
| _version_ | 1811096725572550656 |
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| author | Ziarek, Joshua J. Wagner, Gerhard Wommack, Andrew Tomaras, Jill M Chileveru, Haritha reddy Zhang, Yunfei Nolan, Elizabeth Marie |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Ziarek, Joshua J. Wagner, Gerhard Wommack, Andrew Tomaras, Jill M Chileveru, Haritha reddy Zhang, Yunfei Nolan, Elizabeth Marie |
| author_sort | Ziarek, Joshua J. |
| collection | MIT |
| description | We report the discovery of HD5-CD, an unprecedented C[subscript 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[superscript II]–Cys[superscript IV] (Cys[superscript 5]–Cys[superscript 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. |
| first_indexed | 2024-09-23T16:48:04Z |
| format | Article |
| id | mit-1721.1/109106 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:48:04Z |
| publishDate | 2017 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | mit-1721.1/1091062022-10-03T08:24:15Z Discovery and Characterization of a Disulfide-Locked C[subscript 2]-Symmetric Defensin Peptide Ziarek, Joshua J. Wagner, Gerhard Wommack, Andrew Tomaras, Jill M Chileveru, Haritha reddy Zhang, Yunfei Nolan, Elizabeth Marie Massachusetts Institute of Technology. Department of Chemistry Wommack, Andrew Tomaras, Jill M Chileveru, Haritha reddy Zhang, Yunfei Nolan, Elizabeth Marie We report the discovery of HD5-CD, an unprecedented C[subscript 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[superscript II]–Cys[superscript IV] (Cys[superscript 5]–Cys[superscript 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. United States. National Institutes of Health (DP2OD007045) United States. National Institutes of Health (PO1 GM047467) United States. National Institutes of Health (F32GM103005) United States. National Institutes of Health (EB-002026) National Science Foundation (U.S.) (Grant NSF-007031) 2017-05-16T15:26:43Z 2017-05-16T15:26:43Z 2014-09 Article http://purl.org/eprint/type/JournalArticle 0002-7863 1520-5126 http://hdl.handle.net/1721.1/109106 Wommack, Andrew J., Joshua J. Ziare, Jill Tomaras, Haritha R. Chileveru, Yunfei Zhang, Gerhard Wagner and Elizabeth M. Nolan. "Discovery and Characterization of a Disulfide-Locked C2-Symmetric Defensin Peptide." Journal of the American Chemical Society 136 (October 1 2014) (39): 13494–13497. https://orcid.org/0000-0002-2515-5901 https://orcid.org/0000-0002-6426-2291 https://orcid.org/0000-0002-6153-8803 en_US http://dx.doi.org/10.1021/ja505957w Journal of the American Chemical Society Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society ACS |
| spellingShingle | Ziarek, Joshua J. Wagner, Gerhard Wommack, Andrew Tomaras, Jill M Chileveru, Haritha reddy Zhang, Yunfei Nolan, Elizabeth Marie Discovery and Characterization of a Disulfide-Locked C[subscript 2]-Symmetric Defensin Peptide |
| title | Discovery and Characterization of a Disulfide-Locked C[subscript 2]-Symmetric Defensin Peptide |
| title_full | Discovery and Characterization of a Disulfide-Locked C[subscript 2]-Symmetric Defensin Peptide |
| title_fullStr | Discovery and Characterization of a Disulfide-Locked C[subscript 2]-Symmetric Defensin Peptide |
| title_full_unstemmed | Discovery and Characterization of a Disulfide-Locked C[subscript 2]-Symmetric Defensin Peptide |
| title_short | Discovery and Characterization of a Disulfide-Locked C[subscript 2]-Symmetric Defensin Peptide |
| title_sort | discovery and characterization of a disulfide locked c subscript 2 symmetric defensin peptide |
| url | http://hdl.handle.net/1721.1/109106 https://orcid.org/0000-0002-2515-5901 https://orcid.org/0000-0002-6426-2291 https://orcid.org/0000-0002-6153-8803 |
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