A distinct zinc binding site in the alpha-lactalbumins regulates calcium binding. Is there a physiological role for this control?
A distinct zinc binding site has been found in several alpha-lactalbumin species: bovine, human, guinea pig, and rabbit. Binding of Zn(II) or Al(III) to the calcium forms of these proteins causes exclusion of calcium 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 electron spin resonance by observing free unliganded Mn(II), which was displaced upon Zn(II) binding. Co(II) and Cu(II) were also shown to bind to the zinc site while also expelling Ca(II). The most appropriate model that describes cation binding to alpha-lactalbumins is of two physically distinct but mutually exclusive sites for calcium and zinc, 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 zinc (approximately 50 microM) and calcium (approximately 1 mM), a ca. 40% rate enhancement due to calcium was observed, which was totally accounted for by calcium 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.
D000535:Aluminum / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D003035:Cobalt / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D007700:Kinetics; D007768:Lactalbumin / Q000378:metabolism*; D007785:Lactose / Q000096:biosynthesis; D011817:Rabbits; D015032:Zinc / Q000378:metabolism*
D003035:Cobalt; D003300:Copper; D007768:Lactalbumin; D000535:Aluminum; D007785:Lactose; D015032:Zinc; D002118:Calcium