Metal-binding and nuclease activity of an antimicrobial peptide analogue of the salivary histatin 5.
The salivary antimicrobial peptide histatin 5 is characterized by its cationic nature, structural flexibility, and the presence of two metal-binding sites (the ATCUN motif and a Zn-binding motif). These properties make this peptide a good model for the design of new drugs of low molecular weight. In this work, we have synthesized and studied a new peptide, an analogue of the histatin 5 named ATCUN-C16, which contains both metal-binding centers. The results show that our 20-residue-derived peptide preserves anticandidal activity and exhibits a higher propensity to assume a stable conformation in a hydrophobic environment than do histatin 5 and the C16 peptide that contains the 16 residues of the C-terminal part of histatin 5, although overall our peptide remains a flexible molecule. ACTUN-C16 was found to bind DNA in a gel retardation assay and to have a nuclease activity in the presence of copper and zinc ions and ascorbate. Its nuclease activity can be attributed to the synergistic action of oxidative and hydrolytic activities due to the Cu-ATCUN complex and to the zinc ion coordination, respectively. The results show a new property of this family of salivary peptides and suggest a novel use of this peptide as a small nuclease and biotechnological tool.
Melino
Sonia
S
Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Rome, Italy. melinos@uniroma2.it
Gallo
Mariana
M
Trotta
Edoardo
E
Mondello
Francesca
F
Paci
Maurizio
M
Petruzzelli
Raffaele
R
D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000737:chemistry / Q000378:metabolism*; D002176:Candida albicans / Q000254:growth & development; D003300:Copper / Q000737:chemistry / Q000378:metabolism; D003851:Deoxyribonucleases / Q000737:chemistry / Q000378:metabolism*; D054808:Histatins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009532:Nickel / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D012471:Salivary Proteins and Peptides / Q000737:chemistry / Q000378:metabolism*
D000935:Antifungal Agents; C068075:HTN3 protein, human; D054808:Histatins; D010446:Peptide Fragments; D012471:Salivary Proteins and Peptides; D003300:Copper; D009532:Nickel; D003851:Deoxyribonucleases