CRYSTALLOGRAPHIC ANALYSIS OF O-METHYLTRANSFERASES

O-甲基转移酶的晶体分析

• 批准号: 7370387
• 负责人: JEANNINE R ROSS
• 金额: $ 0.41万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7370387
• 关键词: CRYSTALLOGRAPHIC; ANALYSIS; METHYLTRANSFERASES

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. Plant small molecule O-methyltransferases (OMTs) are ubiquitous throughout the plant kingdom and methylate the hydroxyl and carboxyl moieties of small molecules to form compounds which perform critical functions in plant defense, and in human nutrition and disease prevention. While Type I OMTs methylate the hydroxyl groups of phenylpropanoid compounds to form flavonoids and isoflavonoids, which are known to function in UV protection, and in prevention of human heart disease, cancer, and osteoporosis, Type II OMTs are found in all plants that produce lignin which functions in plant defense, structural support, and provides pulp material for the paper industry. Type III plant OMTs convert small molecule carboxylic acids to their methyl esters, which have been shown to play vital roles in plant defense, signal transduction, floral scent, and development. This group also includes a subset of N-methyltransferases that target the nitrogen functionality of alkaloid small molecules, a group of compounds with important human pharmaceutical benefits. Our lab has made considerable progress in characterizing structures of plant OMTs due to use of the SSRL facility: we recently published the first structures of plant OMTs, those of Chalcone O-methyltransferase (ChOMT) and isoflavone O-methyltransferase (IOMT), two natural product methyltransferases that respectively produce compounds that serve as potent inducers of the soil rhizobia nodulation genes and the major anti-fungal phytoalexin in alfalfa, and the structure of Caffeic acid/5-hydroxyferulic acid 3/5-O-methyltransferase (COMT) from alfalfa, an enzyme involved in lignin biosynthesis. Most recently, the structure of Salicylic acid methyltransferase (SAMT), an enzyme from Clarkia breweri with functions in floral scent and plant defense was solved. Active site modeling of the Jasmonic acid carboxyl methyltransferase (JAMT) from Arabidopsis based on the solved structure of the Clarkia SAMT allowed for the success.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。植物小分子 O-甲基转移酶 (OMT) 在整个植物界中普遍存在，可将小分子的羟基和羧基部分甲基化，形成在植物防御、人类营养和疾病预防中发挥关键功能的化合物。 I 型 OMT 将苯丙类化合物的羟基甲基化，形成类黄酮和异黄酮类化合物，已知它们具有紫外线防护以及预防人类心脏病、癌症和骨质疏松症的功能，而 II 型 OMT 存在于所有产生木质素的植物中它具有植物防御、结构支撑作用，并为造纸工业提供纸浆材料。 III 型植物 OMT 将小分子羧酸转化为其甲酯，这已被证明在植物防御、信号转导、花香和发育中发挥着重要作用。该组还包括 N-甲基转移酶的子集，其靶向生物碱小分子的氮功能，生物碱小分子是一组具有重要人类药学益处的化合物。由于使用了 SSRL 设施，我们的实验室在表征植物 OMT 结构方面取得了相当大的进展：我们最近发表了第一个植物 OMT 结构，即查尔酮 O-甲基转移酶 (ChOMT) 和异黄酮 O-甲基转移酶 (IOMT) 的结构，这两种天然化合物产物甲基转移酶，分别产生作为土壤根瘤菌结瘤基因和苜蓿中主要抗真菌植物抗毒素的有效诱导剂的化合物，以及来自苜蓿的咖啡酸/5-羟基阿魏酸 3/5-O-甲基转移酶 (COMT) 的结构，这是一种参与木质素生物合成的酶。最近，水杨酸甲基转移酶（SAMT）的结构被解析，这是一种来自啤酒克拉克氏菌的酶，具有花香和植物防御功能。基于已解析的 Clarkia SAMT 结构，对拟南芥茉莉酸羧基甲基转移酶 (JAMT) 的活性位点建模取得了成功。