STRUCTURAL AND FUNCTIONAL FEATURES OF THE 5-HT3R BINDING SITE

5-HT3R 结合位点的结构和功能特征

• 批准号: 7719954
• 负责人: Marvin Kenneth Schulte
• 金额: $ 19.32万
• 依托单位: UNIVERSITY OF ALASKA FAIRBANKS
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7719954
• 关键词: Acetylcholine; Binding Proteins; Binding Sites; Biosensor; Chemistry; Class; Computer Retrieval of Information on Scientific Projects Database; Family; Funding; Gated Ion Channel; Goals; Grant; HTR3A gene; Institution; Laboratories; Ligands; Modeling; Neurons; Nicotinic Receptors; Peripheral Nervous System; Pharmacology; Preclinical Drug Evaluation; Proteins; Research; Research Personnel; Resources; Source; Specificity; Structure; Technology; United States National Institutes of Health; Work; abstracting; base; drug discovery; improved; knowledge base; member; receptor; response; sensor

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. Abstract: The primary goal of this project is to develop improved microcantilever-based biosensors using receptor proteins based on an acetylcholine binding protein (AChBP). The AChBP is a soluble protein that displays structure and pharmacology that is strikingly similar to the nicotinic acetylcholine receptor (nAChR) present in the central and peripheral nervous systems. Since the nAChR is a member of a large super-family of ligand gated ion channels (LGICs), this project will ultimately develop sensors that will be useful in high throughput drug screening and drug discovery for this class of neuronal receptors. Aim 1 will evaluate the AChBP itself as a potentially useful biosensor molecule. We will initially demonstrate the use of this sensor in high-throughput drug screening by exploring its interaction with nAChR, GABAR, glycineR and 5-HT3R ligands. Since the AChBP is commonly used as a template for modeling of ligand gated ion channel receptors, an additional benefit of this work will be an expanded knowledge of the basis of ligand specificity at these important receptors. Aim 2 will utilize the AChBP and other receptor proteins to improve sensor response through improved conjugation chemistries in combination with improved microcantilever array technology developed in Dr. Ji's laboratory.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 摘要：该项目的主要目标是使用基于乙酰胆碱结合蛋白（ACHBP）的受体蛋白（ACHBP）开发改进的基于微抗体的生物传感器。 ACHBP是一种可溶性蛋白，显示出与中央和周围神经系统中存在的烟碱乙酰胆碱受体（NACHR）非常相似的结构和药理学。 由于NACHR是配体门控离子通道（LGICS）的大型超级家庭的成员，因此该项目最终将开发该类别的神经元受体的高通量药物筛查和药物发现的传感器。 AIM 1将评估ACHBP本身作为潜在有用的生物传感器分子。我们最初将通过探索其与NACHR，GABAR，甘同能和5-HT3R配体的相互作用来证明该传感器在高通量药物筛查中的使用。 由于ACHBP通常用作建模配体门控离子通道受体的模板，因此这项工作的另一个好处将是对这些重要受体配体特异性基础的扩展知识。 AIM 2将利用ACHBP和其他受体蛋白来通过改进的共轭化学结合结合改进JI博士实验室中开发的Microcantilever阵列技术来改善传感器响应。