Zinc and copper bind to unique sites of histatin 5.
Metal binding has been suggested to be relevant in the antifungal and antibacterial mechanism of histatin 5, a human salivary protein. Proton nuclear magnetic resonance (NMR) spectra were obtained to investigate the specificity of metal binding to the seven histidyl, one aspartyl and one glutamyl amino acid side-chains of histatin 5 in aqueous solutions. Three C(epsilon1)-H histidyl and the C(gamma)-H glutamyl resonances of histatin 5 were selectively altered in spectra of solutions containing three equivalents of zinc. Copper binding to histatin 5 resulted in a reduced intensity of C(beta)-H aspartyl resonances, while no evidence for calcium binding was found. These results indicate that zinc binding to histatin 5 involves His-15 present within the -H-E-X-X-H- zinc binding motif, and copper binding occurs within the N-terminal D-S-H-, ATCUN motif.
Boston University Medical Center, Department of Periodontology and Oral Biology, Boston, MA 02118, USA. grogan@bu.edu
J
J
Grogan
C J
CJ
McKnight
R F
RF
Troxler
F G
FG
Oppenheim
D001224:Aspartic Acid / Q000737:chemistry; D003300:Copper / Q000737:chemistry*; D018698:Glutamic Acid / Q000737:chemistry; D054808:Histatins; D006639:Histidine / Q000737:chemistry; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D011485:Protein Binding; D012471:Salivary Proteins and Peptides / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
C068075:HTN3 protein, human; D054808:Histatins; D008024:Ligands; D012471:Salivary Proteins and Peptides; D001224:Aspartic Acid; D018698:Glutamic Acid; D006639:Histidine; D003300:Copper; D015032:Zinc