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 由乙醇新陈代谢率和乙醇浓度决定 酒精代谢物(乙醛、乙酸盐和NADH)。的水平 这些代谢物是由醇和醛的活性决定的。 代谢酶。结构生物学核心实验室提供了 为合成重组醇和乙醛提供服务 代谢酶及纯品的X射线结晶学分析 蛋白质。在未来的支持期内，此核心还将支持 由独立资助的调查人员进行的研究将 将THIS和分子生物学核心在 前几个资助期。核心的基础性研究问题 是：这是酒精或酒精摄入量的结构性决定因素 醛的氧化和底物对不同人的专一性 酒精和乙醛脱氢酶？研究工具的开发 进一步解决这些重要问题将是服务的重点 由核心在下一个供资期间提供。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 乙醛脱氢酶作为酒精和乙醛的模型 新陈代谢。这些细胞将被用来阐明 测定各种醇和醛的代谢率 (例如，维甲酸)。这些研究将提供更好的理解 已知的酶变异体对酒精代谢的影响以及 乙醇对这种代谢的影响。表达其他蛋白质的细胞 与酒精相关的研究也将产生。