Core C: Protein Chemistry Core

核心C：蛋白质化学核心 蛋白质化学核心将继续为计划项目中的研究小组提供 分离和分析受体片段所需的技术专长和设备 含有全身麻醉剂的光结合部位的。此外，核心还提供 解释蛋白质化学所需的分子建模的计算资源 在受体结构模型方面的结果，并为突变分析的设计提供指导 有必要确定麻醉剂结合的能量贡献。核心在监督之下 科恩博士，位于他的实验室里。核心目前提供的主要设备包括(I)和 应用生物系统492精密自动蛋白质测序仪和在线氨基酸分析仪；和(Ii)2 安捷伦1100高性能可编程控制器，配有紫外光和荧光探测器；和(Iii)安捷伦1100毛细管LC 系统。配体门控离子通道中麻醉剂结合部位的生化表征需要 使用蛋白质化学核心设施中通常不存在的高度专业化的技术 通常不接受用于埃德曼降解或质谱分析的放射性样品。这个 膜蛋白整合体疏水结构域内药物结合部位的鉴定 利用Edman降解法或质量法分离和表征多肽的独特问题 光谱分析。核心的功能是提供适当的设备和高度熟练的蛋白质 化学家可以直接与研究项目互动，制定和开展适当的 研究策略和教育研究人员关于必要的蛋白质化学技术 要么在核心实验室进行，要么在调查员实验室进行。 相关性(请参阅说明)： 大脑中的GABA是许多临床上使用的各种化学麻醉剂的主要作用部位 结构，但麻醉剂结合部位的数量和位置在GABA内或在结构上 相关的烟碱型乙酰胆碱和5-羟色胺5-HT3受体尚不清楚。该核心提供了 识别这些结合位点所需的资源。

CORE C: Protein Chemistry Core The Protein Chemistry Core will continue to provide for the research groups in the Program Project the technical expertise and equipment required for the isolation and sequence analysis of receptor fragments containing the sites of photoincorporation by general anesthetics. In addition, the Core provides computational resources for the molecular modeling that is necessary to interpret the protein chemistry results in terms of models of receptor structure and to provide guidance in the design of mutational analyses necessary to define the energetic contributions to anesthetic binding. The Core is under the supervision of Dr. Cohen and is located in his laboratory. Major equipment cunrently available in the Core include (i) an Applied Biosystems 492 Precise automated Protein Sequenator and in-line amino acid analyzer; and (ii) 2 Agilent 1100 HPLCs equipped with UV and fluorescence detectors; and (iii) an Agilent 1100 capillary LC system. The biochemical characterization of anesthetic binding sites in ligand-gated ion channels requires the use of highly specialized techniques not normally available in protein chemistry core facilities which usually do not accept radioactive samples either for Edman degradation or mass spectrometry. The identification of drug binding sites within the hydrophobic domains of integral membrane proteins poses unique problems for peptide isolation and characterization by either Edman degradation or mass spectrometry. It is the function of the Core to provide the appropriate equipment and highly skilled protein chemists who can interact directly with the research projects to develop and carry out the appropriate research strategies and to educate the investigators about the necessary protein chemistry techniques to be carried out either in the Core or in the investigator's lab. RELEVANCE (See instructions): GABAARS in the brain are a major site of action of many clinically used anesthetics of diverse chemical structure, but the number and location of anesthetic binding sites within GABAARS or in the structurally related nicotinic acetylcholine and serotonin 5-HT3 receptors remains unknown. This Core provides the resources necessary to identify these binding sites.