Cloning the human vitamin D receptor into the pTwin-1 expression vector.

Many of the actions of 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] are mediated by binding to the nuclear vitamin D receptor (VDR). VDR is a member of a superfamily of nuclear receptors that are ligand-dependent transcription factors. Ligand binding induces conformational changes in the VDR that enable the receptor to interact with other coactivators to modulate gene transcription.

Residues of the human nuclear vitamin D receptor that form hydrogen bonding interactions with the three hydroxyl groups of 1alpha,25-dihydroxyvitamin D3.

Most of the biological effects of 1,25-dihydroxyvitamin D(3) (hormone D) are mediated through the nuclear vitamin D receptor (VDR). Hormone binding induces conformational changes in VDR that enable the receptor to activate gene transcription. It is known that residues S237 and R274 form hydrogen bonds with the 1-hydroxyl group of hormone D, while residues Y143 and S278, and residues H305 and H397 form hydrogen bonds with the 3-hydroxyl and the 25-hydroxyl groups of the hormone.

Effect of 25-hydroxyl group orientation on biological activity and binding to the 1alpha,25-dihydroxy vitamin D3 receptor.

The hormonal form of vitamin D, 1alpha,25-dihydroxyvitamin D(3) (1,25D), generates many biological actions by interactions with its nuclear receptor (VDR). The presence of a carbon-25 hydroxyl group is necessary for optimizing binding to the VDR. To examine the effect of spatial orientation of the 25-hydroxyl, two pairs of 22,23-allene sidechain analogs were studied.

Role of residues 143 and 278 of the human nuclear Vitamin D receptor in the full-length and Delta165-215 deletion mutant.

Most of the actions of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] are mediated by binding to the Vitamin D nuclear receptor (VDR). The crystal structure of a deletion mutant (Delta165-215) of the VDR ligand-binding domain (LBD) bound to 1,25(OH)(2)D(3) indicates that amino acid residues tyrosine-143 and serine-278 form hydrogen bonding interactions with the 3-hydroxyl group of 1,25(OH)(2)D(3). Studies of VDR and three mutants (Y143F, S278A, and Y143F/S278A) did not indicate any differences in the binding affinity between the variant receptors and the wild-type receptor.

Flexibility of BIV TAR-Tat: models of peptide binding.

A new approach in determining local residue flexibility from base-amino acid contact frequencies is applied to the twelve million lattice chains modeling BIV Tat peptide binding to TAR RNA fragment. Many of the resulting key features in flexibility correspond to RMSD calculations derived from a set of five NMR derived structures (X. Ye, R.