CONFORMATIONAL CHANGES IN THE VITAMIN D RECEPTOR UPON LIGAND BINDING

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 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. 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.