CORE--STRUCTURAL AND CELLULAR BIOLOGY

核心——结构和细胞生物学

• 批准号: 6563172
• 负责人: WILLIAM F BOSRON
• 金额: $ 13.07万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-01 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6563172
• 关键词: X ray crystallography; alcohol dehydrogenase; alcoholism /alcohol abuse; aldehyde dehydrogenases; biomedical facility; cell biology; chemical kinetics; computer assisted sequence analysis; drug metabolism; enzyme activity; enzyme biosynthesis; enzyme substrate complex; hybrid cells; isozymes; molecular cloning; nucleic acid sequence; peptide chemical synthesis; protein structure function; recombinant proteins; structural biology

The pharmacological and toxicological effects of ethanol are in part determined by the rate of ethanol metabolism and the concentration of alcohol metabolites (acetaldehyde, acetate, and NADH). The levels of these metabolites are determined by the activities of alcohol and aldehyde metabolizing enzymes. The Structural Biology Core laboratory has offered services for the synthesis of recombinant alcohol and aldehyde metabolizing enzymes and for X-ray crystallographic analysis of pure proteins. In the coming period of support, this Core will also support research carried out by investigators with independent funding that will extend observations made by this and the Molecular Biology Core in the previous funding periods. The fundamental research question of the core has been: That are the structural determinants for the rate of alcohol or aldehyde oxidation and the substrate specificity for the different human alcohol and aldehyde dehydrogenases? The development of research tools to further address these important issues will be the focus of services provided by the Core in the coming funding period. The Core will continue to offer the services mentioned above. In particular, it will support the final phase of the crystal structure solution of ALDH2. In a new direction, it will support the generation of cells expressing alcohol and aldehyde dehydrogenases to serve as models of alcohol and aldehyde metabolism. These cells will be utilized to elucidate the factors that determine the rates of metabolism of a variety of alcohols and aldehydes (e.g., retinoids). These studies will provide a better understanding of the effects of the known enzyme variants on alcohol metabolism and the effects of ethanol on this metabolism. Cells expressing other proteins relevant to alcohol research will also be generated.

乙醇的药理和毒理作用部分是 由乙醇代谢速率和乙醇浓度决定 酒精代谢物（乙醛、乙酸盐和 NADH）。 的水平 这些代谢物由酒精和醛的活性决定 代谢酶。 结构生物学核心实验室提供 重组醇和醛的合成服务 代谢酶和纯物质的 X 射线晶体分析 蛋白质。在接下来的支持期间，该Core还将支持 由研究人员在独立资助下进行的研究 扩展本研究和分子生物学核心的观察结果 之前的资助期。 核心的基础研究问题 已经是： 这是酒精率的结构决定因素或 醛氧化和不同人类的底物特异性 乙醇和乙醛脱氢酶？ 研究工具的开发 进一步解决这些重要问题将成为服务重点 由核心在未来的资助期内提供。 核心将继续 提供上述服务。特别是，它将支持 ALDH2 晶体结构溶液的最终相。 在一个新的 方向，它将支持表达酒精和 醛脱氢酶作为醇和醛的模型 代谢。这些细胞将被用来阐明影响因素 测定各种醇和醛的代谢速率 （例如，类维生素A）。 这些研究将提供更好的理解 已知酶变体对酒精代谢的影响以及 乙醇对此代谢的影响。 表达其他蛋白质的细胞 与酒精研究相关的也会产生。