Based on molecular modeling and ligand binding studies, it has been postulated that the vitamin D receptor (VDR) contains two overlapping ligand binding sites, a genomic pocket (VDR-GP) and an alternative pocket (VDR-AP), that mediate rapid responses and regulation of gene transcription, respectively. Our data obtained from molecular mechanics docking studies predict that the major blood metabolite, 25(OH)-vitamin D3 (25D3), selectively bind to the VDR-AP while the steroid hormone 1α,25(OH)2 -vitamin D3 (1,25D3) binds equally well to both pockets, however analog JN prefers the alternative pocket and analog HL is an inhibitor of genomic responses. 1,25D3, 25D3, and JN each rapidly stimulated voltage-gated outwardly rectifying chloride channels (ORCC) in TM4 sertoli cells. Based on molecular modeling and ligand binding studies, it has been postulated that the vitamin D receptor (VDR) contains two overlapping ligand binding sites, a genomic pocket (VDR-GP) and an alternative pocket (VDR-AP), that mediate rapid responses and regulation of gene transcription, respectively. Our data obtained from molecular mechanics docking studies predict that the major blood metabolite, 25(OH)-vitamin D3 (25D3), selectively bind to the VDR-AP while the steroid hormone 1α,25(OH)2 -vitamin D3 (1,25D3) binds equally well to both pockets, however analog JN prefers the alternative pocket and analog HL is an inhibitor of genomic responses. 1,25D3, 25D3, and JN each rapidly stimulated voltage-gated outwardly rectifying chloride channels (ORCC) in TM4 sertoli cells.

Biochemistry