MECHANISM OF GAR TRANSFORMYLASE

描述（研究者摘要）：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制- 依赖性从头嘌呤生物合成酶，甘氨酰胺核苷酸 转化酶 一系列动力学研究，底物特异性 研究、亲和标记研究和定点诱变研究 描述了 这些研究的目的是确定动力学和 转化反应的化学机理，并确定 参与底物结合和催化的酶残基。 这些 研究将提供有关的机制和结构信息 这将为设计特异性的 转化酶抑制剂。 这些研究也将作为 为今后研究酶的相互作用奠定了基础， 构成从头嘌呤生物合成途径和 路径的调节。 尽管已经证明， 抑制该途径显示出癌症化疗的潜力， 关于途径和单个酶的基本信息， 构成的途径仍有待阐明。

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.