Craig S P, McKerrow J H, Newport G R, Wang C C
Department of Pharmaceutical Chemistry, University of California, San Francisco 94143.
Nucleic Acids Res. 1988 Jul 25;16(14B):7087-101. doi: 10.1093/nar/16.14.7087.
Because of the lack of de novo purine biosynthesis, hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) is a critical enzyme in the purine metabolic pathway of the human parasite, Schistosoma mansoni. Using a cDNA clone encoding mouse HGPRTase and subsequently a synthetic oligonucleotide derived from sequencing a clone of genomic DNA, two clones were isolated from an adult schistosome cDNA library. One clone is 1.374 Kilobases (Kb) long and has an open reading frame of 693 bases. The deduced 231 amino acid sequence has 47.9% identity in a 217 amino acid overlap with human HGPRTase. Northern blot analysis indicates that the full length of mRNA for the S. mansoni HGPRTase is 1.45-1.6 Kb. Analysis of the primary structures of the putative active site for human and parasite enzymes reveal specific differences which may eventually be exploitable in the design of drugs for the treatment of schistosomiasis.
由于缺乏从头嘌呤生物合成，次黄嘌呤-鸟嘌呤磷酸核糖转移酶（HGPRTase）是人类寄生虫曼氏血吸虫嘌呤代谢途径中的关键酶。利用编码小鼠HGPRTase的cDNA克隆以及随后从基因组DNA克隆测序中获得的合成寡核苷酸，从成年血吸虫cDNA文库中分离出两个克隆。一个克隆长1.374千碱基（Kb），有一个693个碱基的开放阅读框。推导的231个氨基酸序列在217个氨基酸的重叠区域与人类HGPRTase有47.9%的同一性。Northern印迹分析表明，曼氏血吸虫HGPRTase的mRNA全长为1.45 - 1.6 Kb。对人类和寄生虫酶的假定活性位点的一级结构分析揭示了特定差异，这些差异最终可能在设计治疗血吸虫病的药物时得到利用。
