title: Salivary histatin-5, a physiologically relevant ligand for Ni(II) ions.
abstract: Histatins are a family of human salivary antimicrobial peptides. Histatin-5 (Hst-5, DSHAKRHHGYKRKFHEKHHSHRGY), a prominent member of this family contains an albumin-like, N-terminal Asp-Ser-His sequence, known to bind a Ni(II) ion in a square-planar geometry. Nickel is a strong allergen, and oral exposure to Ni(II) ions can elicit allergic reaction in sensitized persons. In contrast, prior oral exposure to nickel in non-sensitized persons can prevent sensitization. The fate of Ni(II) ions in saliva is obviously important for these processes, yet little is known about it. Using potentiometry, UV-visible titrations and circular dichroism, we determined stability constants for Ni(II) complexes of Hst-5 and two truncated analogs, 5Hst-5 (DSHAK) and 10Hst-5 (DSHAKRHHGY). The conditional binding constant at pH 7.4 for Hst-5 was 10(7.5±0.2), compared to the corresponding value for albumin, 10(6.8±0.3) (M. Sokołowska, A. Krężel, M. Dyba, Z. Szewczuk, W. Bal, Eur. J. Biochem. 269 (2002) 1323-1331). These values indicate that Hst-5 binds Ni(II) five times stronger than HSA. The simulated competition for Ni(II) between Hst-5 and albumin shows that significant amounts of Ni(II) ions may be carried by Hst-5 in vivo. Therefore, Hst-5 and other histatins should be considered as factors in nickel allergy and other forms of nickel toxicity.
authors: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland.
authors: Ewa
authors: E
authors: Kurowska
authors: Arkadiusz
authors: A
authors: Bonna
authors: Grażyna
authors: G
authors: Goch
authors: Wojciech
authors: W
authors: Bal
mesh_terms: D000418:Albumins / Q000378:metabolism; D000595:Amino Acid Sequence; D001667:Binding, Competitive; D002942:Circular Dichroism; D054808:Histatins / Q000138:chemical synthesis / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism*; D007477:Ions / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008969:Molecular Sequence Data; D009532:Nickel / Q000737:chemistry / Q000378:metabolism*; D011199:Potentiometry; D011485:Protein Binding; D012463:Saliva / Q000737:chemistry*; D013057:Spectrum Analysis
chemical_list: D000418:Albumins; C068075:HTN3 protein, human; D054808:Histatins; D007477:Ions; D008024:Ligands; D009532:Nickel