STUDIES ON THE MECHANISM OF GAR TRANSFORMYLASE

描述(调查人员摘要)：本提案概述了一项研究 该计划的目标是确定叶酸的催化机理- 依赖从头合成的嘌呤生物合成酶，甘氨酰胺核糖核苷酸 转化酶。一系列动力学研究，底物专一性 研究、亲和标记研究和定点突变研究 都被描述了。这些研究的目的是定义动力学和 转化反应的化学机理及鉴定 酶残留物参与底物结合和催化作用。这些 研究将提供有关该系统的机械结构信息 这将为特定转化酶的设计提供依据 转化酶抑制剂。这些研究也将作为 为未来研究酶的相互作用奠定了基础 构建新的嘌呤生物合成途径及其机制(S) 对该途径的调控。尽管事实证明， 抑制这一途径显示了癌症化疗的潜力， 有关该途径和每种酶的基本信息 这条途径的构成还有待阐明。

DESCRIPTION (Investigator's Abstract): This proposal outlines a research program whose goal is to determine the catalytic mechanism of the folate- dependent de novo purine biosynthetic enzyme, glycinamide ribonucleotide transformylase. A series of kinetic studies, substrate specificity studies, affinity labeling studies, and site-directed mutagenesis studies are described. The aim of these studies is to define the kinetic and chemical mechanism of the transformylation reaction and to identify the enzyme residues involved in substrate binding and catalysis. These studies will afford mechanistic and structural information about the transformylase which will provide a basis for the design of specific transformylase inhibitors. These studies will also serve as the foundation for future studies on the interactions of the enzymes which constitute the de novo purine biosynthetic pathway and the mechanism(s) of regulation of the pathway. Although it has been demonstrated that inhibition of this pathway shows potential for cancer chemotherapy, much basic information about the pathway and the individual enzymes which constitute the pathway remains to be elucidated.