Brayton K A, Chen Z, Zhou G, Nagy P L, Gavalas A, Trent J M, Deaven L L, Dixon J E, Zalkin H
Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907.
J Biol Chem. 1994 Feb 18;269(7):5313-21.
A cDNA encoding human glutamine phosphoribosylpyrophosphate amidotransferase for step one in de novo purine nucleotide synthesis was cloned, sequenced, and expressed in Chinese hamster ovary cells to yield functional enzyme. Enzyme function was dependent upon removal of an 11-amino-acid propeptide. A mutant enzyme having three propeptide amino acid replacements was not processed and was not active. The human genes GPAT, encoding the amidotransferase, and AIRC, encoding a bifunctional enzyme for steps six and seven in the pathway, were cloned and characterized. GPAT and AIRC are closely linked and divergently transcribed from an intergenic region of approximately 625 base pairs. Expression of a luciferase reporter from the GPAT promoter was approximately 3-4-fold higher than from the AIRC promoter. The GPAT gene was mapped to the q12 region of chromosome 4.
克隆了编码参与嘌呤核苷酸从头合成第一步的人谷氨酰胺磷酸核糖焦磷酸酰胺转移酶的互补DNA（cDNA），对其进行了测序，并在中国仓鼠卵巢细胞中进行表达以产生有功能的酶。酶的功能依赖于去除一个11个氨基酸的前肽。一种具有三个前肽氨基酸替换的突变酶未被加工且无活性。克隆并鉴定了编码酰胺转移酶的人基因GPAT以及编码该途径第六步和第七步双功能酶的AIRC。GPAT和AIRC紧密连锁，从大约625个碱基对的基因间区域反向转录。来自GPAT启动子的荧光素酶报告基因的表达比来自AIRC启动子的表达高约3至4倍。GPAT基因被定位到4号染色体的q12区域。
