STRUCTURAL STUDIES OF ANESTHETIC BINDING SITE IN PROTEIN KINASE C (PKC)

蛋白激酶 C (PKC) 中麻醉剂结合位点的结构研究

• 批准号: 7369502
• 负责人: KEITH W MILLER
• 金额: $ 0.53万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7369502
• 关键词: STRUCTURAL; STUDIES; ANESTHETIC; BINDING; SITE

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. In the USA nearly 25 million patients/year undergo surgery using general anesthetics having very low therapeutic indices and whose molecular mechanisms remain unknown, hampering the design of improved agents. Anesthetics act at high concentrations, which has led to the assumption that the therapeutic binding events were nonspecific. Current views of the molecular mechanisms of anesthesia emphasize anesthetic-protein interactions. The molecular mechanism of general anesthesia remains poorly understood. Anesthetics are relatively nonspecific drugs that interact with transmembrane ion channels and soluble proteins, often causing unwanted side effects. Gaining a detailed understanding of the structural motifs governing anesthetic-protein interactions is a critical step in elucidating the molecular. The long-term objective of this project is to define the molecular determinants of those general anesthetic binding sites that effect the functions of proteins. A detailed understanding of the structural motifs governing protein-anesthetic interactions is a critical step in elucidating the molecular mechanisms underlying general anesthesia. Many of the targets of anesthetics are membrane proteins and difficult to study. However, recently protein kinase C (PKC), has been implicated as a target of anesthetics. We will use the subdomain C1B of PKC, to study the anestheic binding sites.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。在美国，每年有近2500万患者使用治疗指数非常低且分子机制尚不清楚的全麻药进行手术，这阻碍了改进药物的设计。麻醉药在高浓度下起作用，这导致了治疗结合事件是非特异性的假设。目前关于麻醉分子机制的观点强调麻醉剂与蛋白质的相互作用。全身麻醉的分子机制仍然知之甚少。麻醉药是一种相对非特异性的药物，它与跨膜离子通道和可溶性蛋白相互作用，通常会导致不想要的副作用。详细了解控制麻醉剂-蛋白质相互作用的结构基序是阐明分子的关键一步。该项目的长期目标是确定那些影响蛋白质功能的全身麻醉剂结合部位的分子决定因素。对控制蛋白质-麻醉剂相互作用的结构基序的详细了解是阐明全身麻醉的分子机制的关键一步。麻醉药的靶标多为膜蛋白，研究难度较大。然而，近年来，蛋白激酶C(PKC)已被认为是麻醉药的靶点。我们将利用PKC的C1B亚区来研究麻醉药物的结合部位。