STRUCTURE AND MECHANISM OF PLP DEPENDENT ENZYMES

描述 这是一个有竞争力的续约申请， 合作研究酪氨酸酚裂解酶的酶机制。 这种酶使用5 '-周期性磷酸（PLP）作为辅因子，并且它是 参与几种氨基酸修饰反应，包括 转氨、脱羧以及β和γ消除。 几 生物活性代谢物参与多种重要的 生物过程，包括神经传递，依赖于类似的 内切酶 在目前的研究中，合作者将继续他们的研究。 以前的课程，并将产生野生型的三维结构 酪氨酸酚裂解酶与底物和底物类似物。 结构性 这些研究的结果将指导更多的实验， 产生酶的变体形式。 此外，动力学研究 使用多个同位素效应将被用来确定速率限制 酪氨酸酚裂解酶介导催化中的步骤。

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.