Structural studies of phenyl propanoid metabolism

苯丙素代谢的结构研究

• 批准号: 6533521
• 负责人: CHULHEE KANG
• 金额: $ 21.45万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6533521
• 关键词: X ray crystallography; active sites; alcohol dehydrogenase; binding proteins; branched chain aminoacid; computer program /software; crystallization; enzyme activity; enzyme biosynthesis; enzyme mechanism; enzyme structure; enzyme substrate analog; enzyme substrate complex; flavonoids; intermolecular interaction; lignans; oxidoreductase; protein folding; protein sequence; protein structure function; stereochemistry

DESCRIPTION (provided by applicant): The long-term objectives of this research are to establish the detailed nature of the biochemical processes involved in phenylpropanoid metabolism, which together constitutes approximately 30% of the carbon in vascular plants. This includes the enzymes and protein factors involved in biochemical pathways to the medicinally important lignans and isoflavonoids, as well as to the structural plant polymeric lignins. Of these the lignans and isoflavonoids have important roles in human health protection (e.g., chemoprotection against various cancers, in lowering blood cholesterol levels) in treatment of various cancers (e.g., testicular), and in prevention of certain allergies.This particular proposal aims to define the mode of action of the first known protein able to control the binding and orientation of plant phenols (monolignol derived) in order that stereoselective coupling can occur. It is considered that definition of the functional motifs on this protein will aid greatly in identification of other analogous proteins of similar function. Additionally, we wish to examine three aromatic alcohol dehydrogenases involved in key steps to these medicinally important lignans and isoflavonoids, in order to determine how differing enantiospecificity is achieved albeit in each case all going through similar enone intermediates. The primary emphasis of the study will thus employ x-ray crystallographic analysis of each protein with substrates, substrate analogs and inhibitors.

描述（由申请人提供）：这项研究的长期目标是确定苯基丙型类药物代谢涉及的生化过程的详细性质，该过程共同占血管植物中碳的约30％。这包括参与对药物重要的木质和异黄体以及结构性植物聚合物木质素的生化途径的酶和蛋白质因子。在这些中，木烷和异类球体在人类健康保护中具有重要作用（例如，针对各种癌症的化学保护，在降低血液胆固醇水平）中在治疗各种癌症（例如睾丸）中（例如睾丸），以及预防某些特定的建议旨在预防这些特定的建议。定义第一种已知蛋白质的作用方式，能够控制植物酚的结合和方向（单酚衍生）的结合和方向，以便可能发生立体选择偶联。据认为，该蛋白质功能基序的定义将极大地有助于识别其他类似功能的类似蛋白。此外，我们希望检查三种与这些重要的木质脂蛋白和异黄酮类似的关键步骤有关的芳香醇脱氢酶，以确定如何在每种情况下都经过类似的Enone中间体，尽管在每种情况下都如何达到不同的对映异体性。因此，该研究的主要重点将使用底物，底物类似物和抑制剂对每种蛋白质进行X射线晶体学分析。