HYDROXYL RADICAL FOOTPRINTING OF ESTROGEN RECEPTOR-LIGAND & INHIBITOR COMPLEXES

雌激素受体配体的羟基足迹

• 批准号: 8361824
• 负责人: JOSHUA S SHARP
• 金额: $ 0.18万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361824
• 关键词: Binding; Complex; Crystallization; Estrogen Antagonists; Estrogen Receptor Modulators; Estrogen Receptors; Estrogens; Funding; Grant; Hydroxyl Radical; Ligands; Morphologic artifacts; National Center for Research Resources; Pharmaceutical Preparations; Phase; Principal Investigator; Research; Research Infrastructure; Resources; Solutions; Source; Structure; United States National Institutes of Health; X-Ray Crystallography; cost; estrogen-related receptor; hydroxytamoxifen; inhibitor/antagonist

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.

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。 X射线晶体学研究表明，某些抗雌激素药物如羟基他莫昔芬的结合诱导螺旋12的构象变化，这与雌激素结合后的构象变化基本不同。 这种差异被认为是抑制的结构性原因。 然而，相关的雌激素相关受体γ的晶体结构显示出相同的结构，无论是否结合配体或抑制剂。 这个项目的目的是确定是否观察到的差异螺旋12在雌激素受体是一个溶液相现象，或者如果它是一个人工结晶。