CONFORMATIONAL CHANGES IN THE VITAMIN D RECEPTOR UPON LIGAND BINDING

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The binding of different vitamin D derivatives, which show markedly different physiological responses, to the ligand binding domain of the vitamin D receptor (LBDVDR) yield identical structures obtained by X-ray crystallography Previous NMR studies have shown spectral differences for different ligand complexes for the tryptophan located at the ligand binding site residue. We propose to produce three different types of labeled samples [U-2H,13C,15N], [U-2H,12C,15N] and [U-2H,13C,15N] with selected 1H labeled methyl groups of rLBDVDR to study the structural changes and dynamics properties of the protein-ligand complex with different vitamin D derivatives. Many of these methyl containing residues surround the ligand binding site and should be sensitive reporters of differential binding.