Intermediates in the Reactions of Pterin-Dependent Hydroxylases

蝶呤依赖性羟化酶反应中的中间体

• 批准号: 1404129
• 负责人: Paul Fitzpatrick
• 金额: $ 43万
• 依托单位: University of Texas Health Science Center San Antonio
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1404129&HistoricalAwards=false
• 关键词: Intermediates; Reactions; Pterin; Dependent; Hydroxylases

With this award the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Paul Fitzpatrick of the University of Texas Health Science Center-San Antonio to study the mechanism by which oxygen is activated when food is metabolized and converted into new cells and tissues. Molecular oxygen from the air consists of two oxygen atoms bonded together. Living organisms are capable of the incorporation of these atoms in biomolecules, a process that is not spontaneous and that requires the activation of the molecular oxygen. To achieve this goal, they use enzymes that contain metal ions. Dr. Fitzpatrick will study an iron-containing enzyme and pursue the elucidation of intermediates formed upon the chemical interaction between oxygen, the iron-containing enzyme, and the enzyme substrates. The work is having a broad impact on our understanding of the basic chemistry by which oxygen powers living organisms, as well as on the training of the next generation of scientists, including undergraduates who might not otherwise have the opportunity to become involved in scientific research. The goal of the experiments being carried out in this project is to determine previously uncharacterized steps in the activation of oxygen by non-heme pterin-dependent enzymes. A variety of spectroscopic methods are being used to determine the structure of the NO complex of tyrosine hydroxylase with tyrosine and a tetrahydropterin bound as a model for the quaternary complex with oxygen. Rapid-reaction methods are also being used to trap and characterize an intermediate in the reaction of tryptophan hydroxylase and to address the role of proton transfer in cleavage of the oxygen-oxygen bond.

凭借这一奖项，化学分部的生命过程化学项目资助了德克萨斯大学圣安东尼奥健康科学中心的保罗·菲茨帕特里克博士，以研究食物代谢和转化为新细胞和组织时氧气被激活的机制。空气中的氧分子由两个氧原子结合而成。活的有机体能够将这些原子结合到生物分子中，这一过程不是自发的，需要分子氧的激活。为了达到这个目的，他们使用了含有金属离子的酶。菲茨帕特里克博士将研究一种含铁酶，并对氧、含铁酶和酶底物之间的化学相互作用形成的中间体进行阐明。这项工作对我们对氧气为生物体提供动力的基本化学的理解产生了广泛的影响，也对下一代科学家的培训产生了广泛的影响，包括那些可能没有机会参与科学研究的本科生。在这个项目中进行的实验的目标是确定非血红素依赖性蝶素酶激活氧的先前未表征的步骤。各种光谱方法被用来确定酪氨酸羟化酶与酪氨酸和四氢蝶呤结合的NO配合物的结构，作为与氧的四氢蝶呤配合物的模型。快速反应方法也被用于捕获和表征色氨酸羟化酶反应中的中间体，并解决质子转移在氧-氧键裂解中的作用。