Structural studies of phenyl propanoid metabolism

描述(申请人提供)：这项研究的长期目标是确定苯丙烷代谢所涉及的生化过程的详细性质，这些过程加起来约占维管植物碳的30%。这包括生物化学途径中所涉及的酶和蛋白质因子，包括重要的药用木脂素和异黄酮类化合物，以及结构植物聚合木质素。其中，木脂素和异黄酮类化合物在人类健康保护(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)，以及预防某些过敏方面具有重要作用。这项特定的建议旨在定义第一个已知的能够控制植物酚(单酚类)的结合和定位的蛋白质的作用模式，以便发生立体选择性偶联。人们认为，确定该蛋白的功能基序将极大地帮助鉴定其他类似功能的蛋白。此外，我们希望研究参与这些医学上重要的木脂素和异黄酮类化合物的关键步骤的三种芳醇脱氢酶，以确定如何获得不同的对映专一性，尽管在每种情况下都通过相似的烯酮中间体。因此，这项研究的主要重点是对每种蛋白质及其底物、底物类似物和抑制剂进行X射线结晶学分析。

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.