b-Defensin-3 (Human)

Novel Defensin with Broad Spectrum

The human defensins represent an important family of antimicrobial peptides. They are composed of two subclasses: a-defensins such as a-defensin-1 (HNP-1, code 4271-s) and b-defensins (hBD), which are characterized by their distinct arrangement of three disulfide bonds. Following the discovery of hBD-1 (code 4337-s) and hBD-2 (code 4338-s) in 1995 and 1997, respectively, hBD-3 has been included as a new member of this particular family since 2001[J. Biol. Chem., 276, 5707 (2001)].

b-Defensin-3 (Human):
Gly-Ile-Ile-Asn-Thr-Leu-Gln-Lys-Tyr-Tyr-Cys-Arg-Val-Arg-Gly-Gly-Arg-Cys-Ala-Val- Leu-Ser-Cys-Leu-Pro-Lys-Glu-Glu-Gln-Ile-Gly-Lys-Cys-Ser-Thr-Arg-Gly-Arg-Lys-Cys- Cys-Arg-Arg-Lys-Lys
(Disulfide bonds between Cys¹¹-Cys⁴⁰, Cys¹⁸-Cys³³, and Cys²³-Cys⁴¹)

hBD-3 was identified in lesional psoriatic scales, from which hBD-2 was also isolated. Peptide and DNA chemistry revealed hBD-3 to be a 45 amino acid residue peptide. The antimicrobial activity of hBD-3 is characterized by: i) a broad spectrum of antimicrobial activity against many pathogenic microbes such as multi-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium without hemolytic activity, ii) salt-insensitivity up to 200 mM NaCl, iii) expression of activity through cell wall perforation, and iv) regulation by TNF-a and contact with bacteria[J. Biol. Chem., 276, 5707 (2001)]. Later, although the data was obtained using the amino-terminally truncated peptide, hBD-3 (6-45), the following interesting findings were reported: i) hBD-3 is stimulated by interferon-g, and ii) hBD-3 has monocyte activating function and elicits ion channel activity [Cell Tissue Res., 306, 257 (2001)]. It is also reported that unlike hBD-1 and hBD-2 , hBD-3 mRNA expression is inhibited by corticosteroids[Biochem. Biophys. Res. Commun., 280, 522 (2001)]. Significant amounts of these peptides are distributed in the following tissues: skin, tonsil, trachea, placenta, testis, thymus, and heart [J. Biol. Chem., 276, 5707 (2001)], [Cell Tissue Res., 306, 257 (2001)], [Gene, 263, 211 (2001)]. With respect to the structural aspects of hBD-3, an amphipathic dimeric structure was proposed in solution, which is different from those of hBD-1 and hBD-2. This might be responsible for the bactericidal activity against Staphylococcus aureus[J. Biol. Chem., 277, 8279 (2002)].

Thus, the hBD-3, as well as the other defensins, are useful tools for understanding their defense mechanisms against various microorganisms.