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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.