A THALIANA DOUBLE BOND REDUCTASE APO-FORM, BINARY AND TERNARY COMPLEXES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。植物从水生植物到陆生植物的进化伴随着维管植物中大量酚类成分的形成，其中木质素、木脂素和单萜烯含量最为丰富。它们共同在植物防御和细胞壁加固中发挥重要作用，如木脂素具有抗菌、抗真菌、抗病毒和抗氧化特性，而木质素具有支持维管器完整性的结构作用。一些木脂素和单萜衍生物在癌症治疗中得到广泛应用，例如，鬼臼毒素衍生物、天尼泊苷、依托泊苷、依托泊磷和紫杉醇用于治疗生发性睾丸癌和小细胞肺癌，以及某些形式的白血病。其他物质，如肠二醇/肠内酯，被认为具有预防癌症的特性，是通过饮食摄入木脂素（也可能是木质素）前体形成的。该项目的目标是通过高分辨率x射线结构分析来确定木脂素、木质素和单脂素生物合成中这些关键蛋白质和酶的结构功能关系。我们描述和比较了木脂素途径酶，松脂醇-松脂醇还原酶和第二异松脂醇脱氢酶以及各种单酚途径酶(例如，肉桂醇脱氢酶，芳基原双键还原酶，肉桂酰辅酶a还原酶，这些研究结果将为探索生物合成对生态植物保护的调控作用，以及这些药理活性物质在工业规模上的区域特异性和立体特异性合成具有重要意义。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The evolution of plant forms from an aquatic to a land base was accompanied by formation of a vast plethora of phenolic components in the vascular plants, of which the lignins, lignans and monoterpene are the most abundant. Together they play important roles in plant defense and cell wall reinforcement, such as with the lignans having antimicrobial, antifungal, antiviral and antioxidant properties, whereas the lignins have structural roles in support of vascular apparatus integrity. Some lignans and monoterpene derivatives find widespread application in cancer treatment, e.g., the podophyllotoxin derivatives, teniposide, etoposide, etopohos and taxol which are used in treatment of germinal testicular and small cell lung cancers, and for certain forms of leukemia. Others,such as enterodiol/enterolactone, are believed to have cancer-preventing properties and are formed through dietary ingestion of lignans (and possibly lignin) precursors. The goal of this project is thus to define the structure function relationships of these key proteins and enzymes in lignan, lignin and monolignol biosynthesis through high resolution X-ray structural analyses. We describe and compare what is now known about the mechanistic (regiospecificity and enantiospecificity) basis of the lignan pathway enzymes, pinoresinol-lariciresinol reductase and secoisolariciresinol dehydrogenase as well as of various monolignol pathway enzymes (e.g., cinnamyl alcohol dehydrogenase, arylpropenal double bond reductase, cinnamoyl CoA reductase, etc.) The information gained from these studies will be very useful for exploring the regulation of phenylpropanoid biosynthesis for ecological plant protection, and for the industrial-scale regiospecific and stereospecific synthesis of these pharmacologically active substances.