CONFORMATIONAL CHANGES IN THE VITAMIN D RECEPTOR UPON LIGAND BINDING

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 不同的维生素D衍生物的结合，表现出显着不同的生理反应，维生素D受体的配体结合域（LBDVDR）产生相同的结构，通过X射线晶体学以前的NMR研究已经显示光谱差异，为不同的配体复合物的色氨酸位于配体结合位点残基。本研究选择1H标记的rLBDVDR的甲基，制备3种不同类型的标记样品[U-2 H，13 C，15 N]、[U-2 H，12 C，15 N]和[U-2 H，13 C，15 N]，研究不同维生素D衍生物与蛋白质-配体复合物的结构变化和动力学性质。 这些含甲基残基中的许多围绕配体结合位点，并且应该是差异结合的敏感报告物。

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.