ENZYMES OF THIAMIN BIOSYNTHESIS

硫胺素生物合成酶

• 批准号: 7721181
• 负责人: STEVEN E EALICK
• 金额: $ 0.56万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-15 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721181
• 关键词: 5' -adenylyl (beta,gamma-methylene)diphosphonate; Active Sites; Anabolism; Bacteria; Binding; Biochemistry; Catalysis; Complex; Computer Retrieval of Information on Scientific Projects Database; Culture Media; D-xylulose-5-phosphate; Data; Enzymes; Funding; Glyceraldehyde 3-Phosphate; Goals; Grant; Histidine; Institution; Metabolism; Mutate; Neurospora crassa; Orthologous Gene; Paper; Pathway interactions; Peptidylprolyl Isomerase; Phosphorylation; Phosphotransferases; Play; Proteins; Publishing; Pyrimidine; Pyrimidines; Pyruvate; Pyruvates; Research; Research Personnel; Resources; Role; Source; Structure; Sulfur; Thiamin-phosphate kinase; Thiamine; Thiamine Pyrophosphate; Thiazoles; United States National Institutes of Health; Yeasts; aminoimidazole ribotide; analog; base; inorganic phosphate; mutant; pyridoxine; thiaminase II

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. Yeast: Thi4 produces the thiazole moiety in thiamin in yeast. An ortholog of Thi4 in Neurospora crassa binds to the peptidyl-prolyl cis/trans isomerase NcCyP41. NcCyP41 is believed to be responsible for thiamin biosynthesis by inducing a conformational change in Thi4 for product release. The protein Thi5 is required for the biosynthesis of the pyrimidine moiety of thiamin. Thi5 uses pyridoxine and histidine as substrates. Bacteria: TenA has been recently identified as a thiaminase II, which degrades thiamin to pyrimidine and thiazole. The structure of TenA from B. subtilis was determined using data collected at NE-CAT 8BM and the paper was published in Biochemistry in 2005 (A.V. Toms). Key active site residues were mutated based on the structure. Our goal is to determine the structure of the mutants complexed with the substrate thiamin to elucidate the mechanism. The structure complex of ThiSF was solved, and subsequently published in Biochemistry (Lehmann). ThiL, thiamine monophosphate kinase, is the last enzyme in the thiamine biosynthetic pathway. It is responsible for the phosphorylation of thiamine phosphate to yield thiamine pyrophosphate. The goal of this project is to determine the binding mode of the ATP responsible for phosphorylation using the non-hydrolyzable analog AMP-PCP as well as how thiamin monophosphate and thiamin pyrophosphate bind to ThiL for catalysis. ThiC catalyzes the conversion of AIR (5-aminoimidazole ribotide) to the pyrimidine moiety of thiamin, which is the most complex unsolved mechanistic problem in primary metabolism. ThiI and ThiS are proteins involved in the synthesis of the thiazole moiety of thiamin. ThiI may play a role in the sulfur transfer to adenylated ThiS. ThiK, thiamin kinase, is responsible for the salvage of thiamin from the growth medium. DXP (1-deoxy-D-xylulose-5-phosphate) synthase catalyzes the formation of DXP, the precursor to the thiazole moiety of thiamin, from pyruvate and glyceraldehyde-3-phosphate.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 酵母：Thi4在酵母中产生噻唑部分。 Neurospora crassa中Thi4的直系同源物与肽基 - 丙酰基CIS/反式异构酶NCCYP41结合。 据信NCCYP41通过诱导THI4的构象变化以释放产品来负责硫胺素生物合成。蛋白质Thi5是硫胺素嘧啶部分的生物合成所必需的。 Thi5使用吡ido醇和组氨酸作为底物。 细菌：TENA最近被鉴定为硫胺素II，将硫胺素降解为嘧啶和噻唑。 使用NE-CAT 8bm收集的数据确定了枯草芽孢杆菌的Tena结构，该论文于2005年在生物化学中发表（A.V. Toms）。 根据结构突变关键的活性位点残基。 我们的目标是确定与基材硫胺素复合的突变体的结构，以阐明机制。 该F的结构复合物已解决，随后发表在生物化学（Lehmann）中。 Thil，硫胺素单磷酸激酶是硫胺素生物合成途径中的最后一种酶。 它负责硫胺素磷酸盐的磷酸化产生硫胺素焦磷酸盐。 该项目的目的是确定使用不可用的类似物AMP-PCP以及硫胺素单磷酸盐和硫胺素焦磷酸如何与THIL结合Thil进行催化的ATP的结合模式。 Thic催化了硫胺素的空气（5-氨基咪唑核苷酸）向嘧啶部分的转化，这是原代代谢中最复杂的未解决的机械问题。 Thii和这是参与硫胺素硫唑部分的合成的蛋白质。 Thii可能在硫酸转移中发挥作用，以使其对此进行腺苷酸化。 Thiam，硫代激酶，负责从生长培养基中挽救硫胺素。 DXP（1-脱氧-D-氧基5-磷酸）合酶催化DXP的形成，DXP是硫胺素的噻唑部分，来自丙酮酸和甘油醛-3-磷酸的前体。