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

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 在美国，每年有近 2500 万患者使用治疗指数极低的全身麻醉剂进行手术，其分子机制仍不清楚，这阻碍了改进药物的设计。麻醉剂在高浓度下起作用，这导致了治疗结合事件是非特异性的假设。目前对麻醉分子机制的看法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。麻醉剂是相对非特异性的药物，与跨膜离子通道和可溶性蛋白质相互作用，通常会引起不必要的副作用。详细了解控制麻醉剂-蛋白质相互作用的结构基序是阐明该分子的关键一步。该项目的长期目标是确定影响蛋白质功能的全身麻醉剂结合位点的分子决定因素。详细了解控制蛋白质-麻醉相互作用的结构基序是阐明全身麻醉分子机制的关键一步。麻醉剂的许多靶标是膜蛋白，难以研究。然而，最近蛋白激酶 C (PKC) 被认为是麻醉剂的靶标。我们将使用 PKC 的子域 C1B 来研究麻醉剂结合位点。

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.