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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在美国，每年有近2500万患者使用具有非常低的治疗指数的全身麻醉剂进行手术，其分子机制仍然未知，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。目前麻醉的分子机制的观点强调麻醉剂-蛋白质相互作用。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，经常引起不必要的副作用。获得一个详细的了解的结构基序管理麻醉剂蛋白质相互作用是一个关键步骤，阐明分子。本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。详细了解蛋白质与麻醉剂相互作用的结构基序是阐明全身麻醉分子机制的关键步骤。麻醉药的许多靶点是膜蛋白，难以研究。近年来，蛋白激酶C（PKC）被认为是麻醉药的作用靶点。我们将利用PKC的C1 B亚结构域来研究麻醉剂的结合位点。

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.