title: A novel beta-defensin structure: a potential strategy of big defensin for overcoming resistance by Gram-positive bacteria.
abstract: Big defensin is a 79-residue peptide derived from hemocytes of the Japanese horseshoe crab. It has antimicrobial activities against Gram-positive and -negative bacteria. The amino acid sequence of big defensin can be divided into an N-terminal hydrophobic half and a C-terminal cationic half. Interestingly, the trypsin cleaves big defensin into two fragments, the N-terminal and C-terminal fragments, which are responsible for antimicrobial activity against Gram-positive and -negative bacteria, respectively. To explore the antimicrobial mechanism of big defensin, we determined the solution structure of mature big defensin and performed a titration experiment with DPC micelles. Big defensin has a novel defensin structure; the C-terminal domain adopts a beta-defensin structure, and the N-terminal domain forms a unique globular conformation. It is noteworthy that the hydrophobic N-terminal domain undergoes a conformational change in micelle solution, while the C-terminal domain remains unchanged. Here, we propose that the N-terminal domain achieves its antimicrobial activity in a novel fashion and explain that big defensin has developed a strategy different from those of other beta-defensins to suppress the growth of Gram-positive bacteria.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Takahide
authors.initials: T
authors.lastname: Kouno
authors.forename: Naoki
authors.initials: N
authors.lastname: Fujitani
authors.forename: Mineyuki
authors.initials: M
authors.lastname: Mizuguchi
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Osaki
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Nishimura
authors.forename: Shun-ichiro
authors.initials: S
authors.lastname: Kawabata
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Aizawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Demura
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Nitta
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kawano
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D002942:Circular Dichroism; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006434:Hemocytes / Q000378:metabolism; D006737:Horseshoe Crabs / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D017433:Protein Structure, Secondary; D023083:beta-Defensins / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D023083:beta-Defensins