Zinc and copper bind to unique sites of histatin 5

Metal binding has been suggested to be relevant in the antifungal and antib acterial mechanism of histatin 5, a human salivary protein. Proton nuclear magnetic resonance (NMR) spectra were obtained to investigate the specifici ty of metal binding to the seven histidyl, one aspartyl and one glutamyl am ino 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 selectiv ely altered in spectra of solutions containing three equivalents of zinc. C opper binding to histatin 5 resulted in a reduced intensity of CP-H asparty l resonances, while no evidence for calcium binding,vas found. These result s indicate that zinc binding to histatin 5 involves His-15 present within t he -H-E-X-X-H- zinc binding motif, and copper binding occurs within the N-t erminal D-S-H-, ATCUN motif, (C) 2001 Federation of European Biochemical So cieties. Published by Elsevier Science B,V, All rights reserved.