Structural studies of phenyl propanoid metabolism

描述（由申请人提供）：本研究的长期目标是建立涉及苯丙素代谢的生化过程的详细性质，这些过程共同构成维管植物中约30%的碳。这包括酶和蛋白质因子参与生物化学途径的重要药用木脂素和异黄酮，以及结构植物聚合木质素。其中木脂素和异黄酮在保护人体健康（例如，对各种癌症的化学保护，降低血液胆固醇水平），治疗各种癌症（例如，睾丸癌）和预防某些过敏方面具有重要作用。这个特别的提议旨在定义第一个已知的能够控制植物酚（单脂醇衍生）的结合和取向的蛋白质的作用模式，以便发生立体选择偶联。研究认为，确定该蛋白的功能基序将有助于鉴定其他具有类似功能的类似蛋白。此外，我们希望研究三种芳香醇脱氢酶参与这些重要的木脂素和异黄酮的关键步骤，以确定不同的对映体特异性是如何实现的，尽管在每种情况下都通过类似的烯酮中间体。因此，该研究的主要重点将采用x射线晶体学分析每种蛋白质的底物，底物类似物和抑制剂。

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.