STRUCTURAL EVIDENCE FOR THE PRESENCE OF A SECONDARY CALCIUM-BINDING SITE IN HUMAN ALPHA-LACTALBUMIN

The high-resolution X-ray crystal structure of human alpha-lactalbumin (at 1.8 Angstrom) in the presence of an elevated level of calcium rev eals a new secondary calcium binding site, 7.9 Angstrom away from the primary calcium binding site known in all or-lactalbumin structures so far. The new calcium binding site is different from the zinc and sulf ate binding sites [Ren, J., et al. (1993) J. Biol. Chem. 268, 19292-19 298] but shares common features with the manganese binding site as des cribed by Gerkin [Gerkin, T. A. (1984) Biochemistry 23, 4688-4697]. Th e proximity of the manganese and calcium binding region and the locati on of the functional site on one side of the charged surface of the al pha-lactalbumin molecule suggest that these binding sites might play a role in the formation of the lactose synthase complex.