Ai. Bush et al., A NOVEL ZINC(II) BINDING-SITE MODULATES THE FUNCTION OF THE BETA-A4 AMYLOID PROTEIN-PRECURSOR OF ALZHEIMERS-DISEASE, The Journal of biological chemistry, 268(22), 1993, pp. 16109-16112
Abnormalities of zinc metabolism occur in Alzheimer's disease (AD), a
condition where pathological catabolism of the amyloid protein precurs
or (APP) causes cerebral betaA4 amyloidosis. An association between zi
nc and ApP metabolism was sought by studying the binding of Zn-65(2+)
to APP. Zn-65(2+) bound in a rapid, saturable, and specific manner (K(
D) = 764 nM). A novel zinc binding motif, strongly conserved between m
embers of the APP family, was located between the cysteine-rich and ne
gatively charged domains of the protein. Zinc increased binding of ''P
to heparin and has been shown to potentiate the inhibition of coagula
tion factor XIa by an APP isoform containing a Kunitz-type inhibitory
domain (Komiyama, Y., Murakami, T., Egawa, H., Okubo, S., Yasunaga, K.
, and Murata, K. (1992) Thromb. Res. 66,397-408) situated near the zin
c binding region. Zinc is a factor that modulates the functional prope
rties of the substrate for betaA4 amyloidogenesis.