CONFORMATIONAL CHANGES IN THE VITAMIN D RECEPTOR UPON LIGAND BINDING

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 不同的维生素D衍生物与维生素D受体(LBDVDR)的配体结合域的结合产生了相同的结构。以前的核磁共振研究表明，不同的配体复合体对位于配体结合位点残基的色氨酸具有不同的光谱差异。我们建议用rLBDVDR的1H标记甲基制备三种不同类型的标记样品[U-2H，13C，15N]，[U-2H，12C，15N]和[U-2H，13C，15N]，以研究不同维生素D衍生物与蛋白质-配体络合物的结构变化和动力学性质。其中许多甲基残基围绕着配体结合部位，应该是差异结合的敏感报告。

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.