ENZYMES OF AMINO ACID BIOSYNTHESIS

氨基酸生物合成酶

• 批准号: 7955095
• 负责人: STEVEN E EALICK
• 金额: $ 0.25万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955095
• 关键词: 3-dehydroquinate; Active Sites; Archaea; Aromatic Amino Acids; Computer Retrieval of Information on Scientific Projects Database; Cysteine; Environment; Enzymes; Funding; Grant; Inorganic Sulfates; Institution; Mycobacterium tuberculosis; Orthologous Gene; Oxidants; Oxidative Stress; Paper; Pathway interactions; Phagocytosis; Proteins; Publishing; Reporting; Research; Research Personnel; Resources; Source; Structure; Sulfides; Sulfur; System; Ubiquitin Like Proteins; United States National Institutes of Health; Unspecified or Sulfate Ion Sulfates; aminoacid biosynthesis; catalyst; enzyme structure; flexibility; inorganic phosphate; macrophage; structural biology

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. Mycobacterium tuberculosis utilizes a sulfur transfer protein mechanism to biosynthesize cysteine when exposed to the oxidative stress environment upon phagocytosis by a macrophage. This system involves the proteins Rv1335 (CysO) and Rv1336 (CysM). An alternative pathway to cysteine in M. tuberculosis exists, but uses sulfide as the sulfur source, which is readily oxidized to sulfate when exposed to oxidizing agents. M. tuberculosis has evolved the ability to utilize a ubiquitin like protein as a sulfur transfer protein, CysO, to serve as the sulfur source by generating a less reactive thio-caryboxy C-terminus. CysO is able to deliver the sulfur atom through its flexible digylcyl C-terminus into the active site of CysM, which is a pyridoxyl 5'-phosphate utilizing b-elimination enzyme. In Archaea, orthologous genes responsible for the first two steps of the aromatic amino acid biosynthesis leading to 3-dehydroquinate (DHQ) are missing. Recently, two protein products from Methanocaldococcus jannaschii, Mj0400 and Mj1249, have been reported as the nonorthologous catalysts of the DHQ formation. Crystal structures of these enzymes assisted the identification of the substrates and the elucidation of their catalytic mechanisms. Structures have been solved and papers published.

这个子项目是许多利用 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 中心，但不一定是研究者所在的机构。 结核分枝杆菌利用硫转移蛋白机制，当暴露于氧化应激环境时，通过巨噬细胞的吞噬作用来生物合成半胱氨酸。 该系统涉及蛋白质Rv 1335（CysO）和Rv 1336（CysM）。 在M.结核病是存在的，但使用硫化物作为硫源，当暴露于氧化剂时，硫化物容易氧化成硫酸盐。 M.结核病已经进化出利用泛素样蛋白作为硫转移蛋白CysO的能力，通过产生反应性较低的硫羧基C-末端作为硫源。 CysO能够将硫原子通过其柔性二羟甲基C-末端递送到CysM的活性位点，CysM是一种利用β-消除酶的吡哆5 ′-磷酸。在拟南芥中，缺失了负责芳香族氨基酸生物合成的前两个步骤，导致3-脱氢奎尼酸（DHQ）的正向同源基因。 最近，来自詹氏甲烷球菌的两种蛋白质产物Mj 0400和Mj 1249已被报道为DHQ形成的非邻苯二甲酸催化剂。 这些酶的晶体结构有助于鉴定底物和阐明其催化机制。结构已被解决和论文发表。