HYDROXYL RADICAL FOOTPRINTING OF ESTROGEN RECEPTOR-LIGAND & INHIBITOR COMPLEXES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 X射线结晶学研究表明，某些抗雌激素药物如羟基他莫昔芬的结合会导致螺旋12的构象变化，这与雌激素结合时的构象变化有很大不同。这种差异被认为是抑制的结构性原因。然而，无论是配体还是抑制剂被结合，相关的雌激素相关受体伽马的晶体结构都显示出相同的结构。这个项目的目的是确定观察到的雌激素受体螺旋12的差异是溶液相现象，还是结晶的产物。

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. X-ray crystallography studies show that binding of certain antiestrogen drugs like hydroxytamoxifen induce a conformational change in helix 12 that is substantially different from the conformational change upon binding of estrogen. This difference is presumed to be the structural cause of inhibition. However, the crystal structures of the related estrogen-related receptor gamma shows an identical structure regardless of whether the ligand or the inhibitor is bound. The purpose of this project is to determine if the observed differences in helix 12 in the estrogen receptor is a solution-phase phenomenon, or if it is an artifact of crystallization.