A distinct zinc-binding site in the .alpha.-lactalbumins regulates calcium binding. Is there a physiological role for this control?

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Abstract
A distinct Zn binding site was found in several .alpha.-lactalbumin species: bovine, human, guinea pig and rabbit. Binding of Zn(II) or Al(III) to the Ca forms of these proteins causes exclusion of Ca and return of the protein to its apo conformation as determined by fluorescence emission spectral parameters. Zn(II) and Al(III) dissociation constants are in the low micromolar range. In addition, determinations of Zn(II) binding were made by ESR by observing free unliganded Mn(II), which was displaced upon Zn(II) binding. Co(II) and Cu(II) also bound to the Zn site while expelling Ca(II). The most appropriate model that describes cation binding to .alpha.-lactalbumins is of 2 physically distinct but mutually exclusive sites for Ca and Zn, respectively, where the protein cannot bind cations at both sites simultaneously. Kinetic parameters for lactose biosynthesis show absolutely no difference between the apo or Zn(II) and Ca(II) forms of .alpha.-lactalbumin. At physiological concentrations of Zn (.apprx. 50 .mu.M) and Ca (.apprx. 1 mM), a .apprx. 40% rate enhancement due to Ca was observed, which was totally accounted for by Ca activation of galactosyl transferase. While either conformer of .alpha.-lactalbumin [Ca(II) or Zn(II)] is kinetically equivalent, the Ca(II) form probably dominates under physiological conditions.