Nuclear vitamin K2 binding protein in human osteoblasts -: Homologue to glyceraldehyde-3-phosphate dehydrogenase

The importance of vitamin K in bone metabolism has been suggested previously. The binding protein of vitamin K-2 (menatetrenone, 2-methyl-3-all-trans-tetraphenyl-1,4-naphthoquinone, menaquinone-4), found in nuclear extract of human osteoblasts, binds to vitamin K-1 and K-2, but not K-3. Since the binding protein does not bind to other steroids or vitamins, such as hydrocortisone, vitamin A, 1,25(OH)(2)vitamin D-3, trolox (a derivative of vitamin E), and warfarin, a specific binding protein to vitamin K-1 and vitamin K-2 in osteoblasts was suggested. The size of the specific binding protein was revealed to be 6S by sucrose density gradient and about 40,000 daltons by SDS-PAGE. Twenty amino acid residues from the N-terminal were the same as human glyceraldehyde-3-phosphate dehydrogenase (GAPDH), but the 21st residue, alanine, was replaced with serine. The binding protein was precipitated with anti-human GAPDH antibody, and authentic human GAPDH could bind vitamin K-2. We propose that the nuclear binding protein for vitamin K-2 exists in nuclei similarly to other vitamin receptors and that the molecular structure is very close to human GAPDH. (C) 1999 Elsevier Science Inc.