PURE UNDER CARBON DIOXIDE

纯净低于二氧化碳

• 批准号: 7954300
• 负责人: IRIMPAN I MATHEWS
• 金额: $ 0.21万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954300
• 关键词: Acids; Biochemical; Carbamates; Carbon Dioxide; Carboxyamidotriazole; Chickens; Computer Retrieval of Information on Scientific Projects Database; Enzymes; Escherichia coli; Escherichia coli Proteins; Eukaryota; Funding; Genomics; Grant; Hand; Histidine; Imidazole; Institution; Metabolic Pathway; Mutase; Prokaryotic Cells; Purines; Reaction; Research; Research Personnel; Resources; Ribonucleotides; Source; Structure; United States National Institutes of Health; Work; fungus; mutant; protonation; purine; structural biology; synchrotron radiation

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. Biochemical studies and genomic analyses of the Escherichia coli and Gallus gallus carboxyaminoimidazole ribonucleotide synthases (PurEs) indicate that these purine biosynthetic enzymes provide an unusual example of evolutionary divergence in a highly conserved, primary metabolic pathway. Class I PurEs, typified by the E. coli protein and found in most prokaryotes and fungi, catalyze the reversible transfer of a CO(2) group from the carbamate of N5-carboxyamino imidazole ribonucleotide (N5-CAIR) to C4, yielding 4-carboxy aminoimidazole ribonucleotide (CAIR). On the other hand, class II PurEs, typified by the G. gallus enzyme and found in higher eukaryotes, form CAIR by reversible transfer of CO(2) to aminoimidazole ribonucleotide (AIR). The current structural study involves class I PurE (N5-carboxyaminoimidazole mutase) with an emphasis on its chemically unique mutase reaction. A working mechanistic hypothesis involves a histidine (His45 in E. coli PurE) functioning as a general acid, but no evidence for multiple protonation states has been obtained. The structural study will be very important for getting a better understanding of the mechanism. We are in particular studying the structures of the mutants of His45.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 对大肠杆菌和原鸡羧氨基咪唑核糖核苷酸合酶 (PurEs) 的生化研究和基因组分析表明，这些嘌呤生物合成酶在高度保守的初级代谢途径中提供了进化分歧的不寻常例子。 I 类 PurE 以大肠杆菌蛋白为代表，存在于大多数原核生物和真菌中，催化 CO(2) 基团从 N5-羧基氨基咪唑核糖核苷酸 (N5-CAIR) 的氨基甲酸酯到 C4 的可逆转移，产生 4-羧基氨基咪唑核糖核苷酸 (CAIR)。另一方面，以原鸡酶为代表并在高等真核生物中发现的 II 类 PurE 通过将 CO(2) 可逆转移到氨基咪唑核糖核苷酸 (AIR) 来形成 CAIR。 目前的结构研究涉及 I 类 PurE（N5-羧氨基咪唑变位酶），重点是其化学上独特的变位酶反应。 一种工作机制假设涉及组氨酸（大肠杆菌 PurE 中的 His45）作为一般酸发挥作用，但尚未获得多种质子化状态的证据。 结构研究对于更好地理解该机制非常重要。 我们正在特别研究 His45 突变体的结构。