title: Discovery and characterization of a disulfide-locked C(2)-symmetric defensin peptide.
abstract: We report the discovery of HD5-CD, an unprecedented C2-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.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wommack
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Ziarek
authors.forename: Jill
authors.initials: J
authors.lastname: Tomaras
authors.forename: Haritha R
authors.initials: HR
authors.lastname: Chileveru
authors.forename: Yunfei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wagner
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Nolan
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D023084:alpha-Defensins / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; C500225:DEFA5 protein, human; D004220:Disulfides; D023084:alpha-Defensins