(American Chemical
Society, 2014) Wommack, Andrew
J.; Ziarek, Joshua J.; Tomaras, Jill; Chileveru, Haritha R.; Zhang, Yunfei; Wagner, Gerhard; Nolan, Elizabeth M.
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 CysII–CysIV (Cys5–Cys20) 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.
