GLUTAMINE AMIDOTRANSFERASE STRUCTURE/FUNCTION/REGULATION

谷氨酰胺转移酶是一个酶家族，它利用 生物合成中的谷氨酰胺酰胺。它们提供了以下主要途径 氮在氨基酸、嘌呤和嘧啶中的结合 核苷酸、氨基糖和辅酶。有3种谷氨酰胺 嘌呤核苷酸合成途径中的氨基转移酶。 谷氨酰胺PRPP氨基转移酶催化第一步，是关键 从头开始途径中的调节酶。的长期目标是 本研究旨在探讨谷氨酰胺的基本作用机制。 氨基转移酶的催化与调控及基因调控 微生物。有4个具体目标。(一)确定工作机制 谷氨酰胺PRPP氨基转移酶的调节。这些实验的重点是 两个调控事件：核苷酸终产物抑制和加工 枯草芽孢杆菌酶中NH2末端的前肽。(2) 确定大肠杆菌基因的遗传调控机制 参与IMP向AMP和GMP分支的通路。(三)确定 嘌呤碱基如何与大肠杆菌pur调节子抑制子结合以及这如何 结合促进特定的全息抑制子-DNA相互作用。(4) 枯草杆菌转录调控机制的确定 编码通向IMP的10步途径的PUR操纵子及其调控 IMP到AMP和GMP分支的Pura、guaA和guaB基因。最后， 计划进行实验以确定枯草杆菌的重要性 操纵子基因重叠在建立蛋白质翻译化学计量学中的作用 酶的合成。嘌呤代谢一直是一个肥沃的领域 开发治疗多种疾病的药物。两种抗癌药物 嘌呤途径中的谷氨酰胺氨基转移酶、酸性蛋白和 三氯核苷具有抗肿瘤活性。

Glutamine amidotransferases are a family of enzymes that utilize the amide of glutamine in biosynthesis. they provide the main route for incorporation of nitrogen into amino acids, purine and pyrimidine nucleotides, amino sugars and coenzymes. There are 3 glutamine amidotransferases in the pathway for purine nucleotide synthesis. Glutamine PRPP amidotransferase catalyzes step 1 and is the key regulatory enzyme in the de novo pathway. The long term objective of this research is to determine basic mechanisms for glutamine amidotransferase catalysis and regulation as well as gene regulation in microorganisms. There are 4 specific aims. (1) Determine mechanisms for regulation of glutamine PRPP amidotransferase. The experiments focus on two regulatory events: nucleotide endproduct inhibition and processing of an NH2-terminal pro-peptide in the Bacillus subtilis enzyme. (2) Determine mechanisms for genetic regulation of Escherichia coli genes involved in the IMP to AMP and GMP branches of the pathway. (3) Determine how purine bases bind to E. coli pur regulon aporepressor and how this binding promotes the specific holorepressor-DNA interactions. (4) Determine mechanisms for transcriptional regulation of the B. subtilis pur operon which encodes the 10 step pathway to IMP and regulation of genes purA, guaA and guaB for the IMP to AMP and GMP branches. Finally, experiments are planned to determine the importance of B. subtilis pur operon gene overlaps in establishing the translational stoichiometry for enzyme synthesis. Purine metabolism has been a fertile area for development of drugs against a variety of diseases. Two inhibitors of glutamine amidotransferases in the purine pathway, acivicin and triciribine have antineoplastic activity.