STRUCTURE-FUNCTION RELATIONSHIP OF ISOFLAVONOID O-METHYLTRANSFERASES

异黄酮O-甲基转移酶的结构-功能关系

• 批准号: 8170629
• 负责人: CHANG-JUN LIU
• 金额: $ 0.41万
• 依托单位: BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170629
• 关键词: Anabolism; Biochemical; Biochemical Genetics; Complex; Computer Retrieval of Information on Scientific Projects Database; Disease; Enzymes; Fabaceae; Family; Family member; Flavonoids; Funding; Grant; Habits; Insecta; Institution; Lead; Mediating; Medicago truncatula; Metabolic; Metabolism; Methylation; Methyltransferase; Molecular; Mutagenesis; Pathway interactions; Plant Model; Plants; Play; Process; Property; Proteins; Research; Research Personnel; Resistance; Resources; Rhizobium; Roentgen Rays; Role; Signal Transduction; Source; Stress; Structure; Structure-Activity Relationship; United States National Institutes of Health; base; in vivo; pathogen; positional cloning; sample fixation; ultraviolet irradiation

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. Due to their sessile habit, plants have evolved a complex set of secondary metabolites to protect them from diseases, herbivory and many other environmental stresses. We are employing a combined protein crystallographic/biochemical-genetics approach to understand the details of structures and functions of the key biosynthetic enzymes that underlie the diversity of secondary metabolism. Our current focus involves a group of S-adenosylmethionine (SAM) dependent O-methyltransferases, enzymes that facilitate methylation of polyphenolic (iso)flavoniods (flavonoids and isoflavonoids). Specific methylated forms of (iso)flavonoids have been shown to mediate many processes including resistance to UV irradiation, fungal pathogens, insect attack, and plant-rhizobium signaling for N2 fixation. We recently identified a small family of (iso)flavonoid O-methyltransferases (IOMTs) from the legume model plant Medicago truncatula. However the structural underpinnings governing their biochemical properties are not completely understood, and the catalytic roles these enzymes play in planta remain to be defined. We propose a combined X-ray crystallographic and mutagenesis approach to explore the structural basis for their regiospecific and stereoselective methylations. We also propose to use reverse genetics and metabolic profiling to assess the in vivo functions of the specific IOMT family members for (iso)flavonoid biosynthesis. These structure and function analyses will lead to a more complete understanding of the molecular basis that underlies the complexity of (iso)flavonoid biosynthetic pathways.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 由于它们的无柄习性，植物已经进化出一套复杂的次生代谢产物，以保护它们免受疾病、食草动物和许多其他环境胁迫的影响。 我们正在采用蛋白质晶体学/生物化学遗传学相结合的方法来了解构成次级代谢多样性基础的关键生物合成酶的结构和功能的细节。 我们目前的重点涉及一组S-腺苷甲硫氨酸（SAM）依赖的O-甲基转移酶，酶，促进多酚（异）黄酮类化合物（类黄酮和黄酮）的甲基化。 已证明（异）黄酮的特定甲基化形式介导许多过程，包括对紫外线照射、真菌病原体、昆虫攻击的抗性以及植物-根瘤菌固定N2的信号传导。我们最近确定了一个小家族的（异）黄酮O-甲基转移酶（IOMTs）从豆科模式植物蒺藜苜蓿。 然而，控制其生化特性的结构基础尚未完全了解，这些酶在植物中发挥的催化作用仍有待确定。 我们提出了一种结合X射线晶体学和诱变方法来探索其区域特异性和立体选择性甲基化的结构基础。我们还建议使用反向遗传学和代谢谱来评估特定IOMT家族成员（异）类黄酮生物合成的体内功能。这些结构和功能的分析将导致更完整的理解的分子基础，（异）类黄酮生物合成途径的复杂性。