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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 X射线晶体学研究表明，某些抗雌激素（如羟基酰昔芬）的结合诱导螺旋12中的构象变化，这与雌激素结合时构象变化大不相同。 假定这种差异是抑制的结构原因。 然而，与雌激素相关受体伽马相关的晶体结构显示出相同的结构，无论配体还是抑制剂是结合的。 该项目的目的是确定雌激素受体中观察到的螺旋12中观察到的差异是溶液 - 相现象，还是它是结晶的伪像。