STRUCTURE AND MECHANISM OF PLP DEPENDENT ENZYMES

PLP依赖性酶的结构和机制

• 批准号: 2627556
• 负责人: ROBERT STEPHEN PHILLIPS
• 金额: $ 2.44万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2627556
• 关键词: X ray crystallography; aminoacid metabolism; carbon carbon lyase; chemical kinetics; enzyme mechanism; enzyme structure; enzyme substrate; hydrolase; kynurenine; mutant; nonradiation isotope effect; phenols; pyridoxal phosphate; site directed mutagenesis; stop flow technique; tryptophanase; tyrosine

DESCRIPTION This is a competitive renewal application to provide continued support for collaborative studies on the enzymatic mechanisms of tyrosine phenol-lyase. This enzyme uses 5'-periodical phosphate (PLP) as a cofactor, and it is involved in several amino acid modification reactions including transaminations, decarboxylations and beta and gamma eliminations. Several biologically active metabolites involved in a variety of important biological processes, including neurotransmission, depend on similar enzymes. In the present studies the collaborators will continue on their previous course and will generate three dimensional structures of wild-type tyrosine phenol-lyase with substrates and substrate analogs. The structural results of these studies will guide additional experiments for the generation of variant forms of the enzyme. In addition, kinetic studies using multiple isotope effects will be done to identify the rate limiting step in tyrosine phenol-lyase mediated catalysis.

描述 这是一项具有竞争力的续订申请，将继续提供以下支持 酪氨酸苯酚裂解酶作用机理的协同研究。 这种酶使用5‘-周期性磷酸(PLP)作为辅因子，它是 参与了几个氨基酸修饰反应，包括 转氨基、脱羧基、贝塔和伽马消除。几个 生物活性代谢物参与了多种重要的 生物过程，包括神经传递，依赖于类似的 酵素。在目前的研究中，合作者将继续他们的 之前的课程，并将生成野生类型的三维结构 酪氨酸苯酚裂解酶及其底物类似物。结构性的 这些研究的结果将指导进一步的实验 酶的变异形式的产生。此外，动力学研究 将使用多个同位素效应来识别速率限制 酪氨酸苯酚裂解酶介导的催化。