GLUTAMINE AMIDOTRANSFERASE STRUCTURE/FUNCTION/REGULATION

谷氨酰胺酰胺转移酶是利用谷氨酰胺转移酶的酶家族。 谷氨酰胺在生物合成中的作用。它们提供了 氮掺入氨基酸、嘌呤和嘧啶中 核苷酸、氨基糖和辅酶。 有3个谷氨酰胺 嘌呤核苷酸合成途径中的酰胺转移酶。 谷氨酰胺PRPP转酰胺酶催化第1步， 调节酶在从头途径。 的长期目标 本研究旨在确定谷氨酰胺的基本机制， 酰胺转移酶的催化和调控以及基因调控， 微生物的 有四个具体目标。(1)确定机制， 谷氨酰胺PRPP酰胺转移酶的调节。 实验的重点是 两个调节事件：核苷酸终产物抑制和 枯草芽孢杆菌酶中的NH 2末端前肽。（二） 确定大肠杆菌基因的遗传调控机制 参与IMP至AMP和GMP通路分支。(3)确定 嘌呤碱基如何与E.大肠杆菌pur调节子脱辅基阻遏物， 结合促进特异性的holorepressor-DNA相互作用。（四） 确定B的转录调节机制。枯草 pur操纵子，编码IMP的10步途径， IMP至AMP和GMP分支的基因purA、guaA和guaB。 最后， 计划进行实验以确定B的重要性。枯草蛋白酶 操纵子基因重叠在建立翻译化学计量学 酶合成 嘌呤代谢一直是一个肥沃的领域， 开发针对多种疾病的药物。 两种抑制剂 嘌呤途径中的谷氨酰胺转移酶，阿西维辛和 曲西立滨具有抗肿瘤活性。

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.