文章摘要
余志会 1,2,方肆云 3,孙铭飞 1,戚南山1,刘文俊 2,李 娟 1,胡俊菁 1,廖申权 1.寄生原虫嘌呤磷酸核糖转移酶研究进展[J].广东农业科学,2023,50(8):163-172
查看全文    HTML 寄生原虫嘌呤磷酸核糖转移酶研究进展
Research Advances in Purine Phosphoribosyltransferases of Protozoan Parasites
  
DOI:10.16768/j.issn.1004-874X.2023.08.017
中文关键词: 寄生原虫  腺嘌呤磷酸核糖转移酶  次黄嘌呤 - 鸟嘌呤 - 黄嘌呤磷酸核糖转移酶  嘌呤核苷酸  药物靶标  抑制剂
英文关键词: protozoan parasites  adenine phosphoribosyltransferase  hypoxanthine-guanine-xanthine phosphoribosyltransferase  purine nucleotide  drug target  inhibitors
基金项目:广东省农业科学院科技创新战略专项资金(高水平农科院建设)(XTXM202202,202122TD);广东省基础与应用基础研究基金(2021A1515012401,2021A1515010521)
作者单位
余志会 1,2,方肆云 3,孙铭飞 1,戚南山1,刘文俊 2,李 娟 1,胡俊菁 1,廖申权 1 1. 广东省农业科学院动物卫生研究所 / 农业农村部禽流感等家禽重大疫病防控重点实验室 /广东省畜禽疫病防治研究重点实验室广东 广州 5106402. 仲恺农业工程学院动物科技学院广东 广州 510225 3. 温氏食品集团股份有限公司广东 云浮 527400 
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中文摘要:
      寄生原虫是一类单细胞寄生性原虫,包括利什曼原虫(Leishmania spp.)、锥虫(Trypanosoma spp.)、疟原虫(Plasmodium spp.)、刚地弓形虫(Toxoplasma gondii)、隐孢子虫(Cryptosporidium spp.)和艾美耳球虫(Eimeria spp.)等,可引起严重危害人类与动物健康以及对养殖业造成巨大经济损失的原虫病。寄生虫入侵宿主后的发育和繁殖需要大量的嘌呤核苷酸,相应的嘌呤碱基在嘌呤磷酸核糖转移酶的催化下生成对 应的嘌呤核苷酸。嘌呤磷酸核糖转移酶是一类参与嘌呤核苷酸补救合成的重要代谢酶,广泛存在于寄生原虫中。寄生原虫的嘌呤磷酸核糖转移酶主要包括腺嘌呤磷酸核糖转移酶和次黄嘌呤 - 鸟嘌呤 - 黄嘌呤磷酸核糖转移酶,两者在寄生原虫中分别催化腺嘌呤核苷酸、次黄嘌呤核苷酸、鸟嘌呤核苷酸和黄嘌呤核苷酸合成,从而参与寄生原虫的多个生化代谢过程,不仅为寄生原虫核酸生物合成等提供前体物质,还为虫体提供通用能量载体。由于寄生原虫的嘌呤补救途径明显区别于宿主的从头合成途径,且嘌呤磷酸核糖转移酶是寄生原虫嘌呤补救途径的关键酶,因而近年来寄生原虫嘌呤磷酸核糖转移酶成为抗原虫药物候选靶标的研究热点,以寄生原虫嘌呤磷酸核糖转移酶为潜在靶标,特异性筛选、设计抑制剂,并开发抗寄生原虫药物取得重要进展。以利什曼原虫、锥虫、疟原虫和弓形虫的嘌呤磷酸核糖转移酶为重点,综述寄生原虫嘌呤磷酸核糖转移酶的基本特征、生物学功能、抑制剂筛选与应用的研究进展,以期为抗寄生原虫药物靶标研究与新型抑制剂筛选提供参考。
英文摘要:
      Parasitic protozoa are single-celled organisms that have adapted to live in cells of humans and animals. The protozoan parasites include Leishmania spp., Trypanosoma spp., Plasmodium spp., Toxoplasma gondii, Cryptosporidium spp., and Eimeria spp., which can cause protozoal diseases that seriously endanger human and animal health and cause huge economic losses in the livestock industry. Parasite development and reproduction after invasion of the host require a large number of purine nucleotides, and the corresponding purine bases are catalyzed by purine phosphoribosyl transferase to generate the corresponding purine nucleotides. Purine phosphoribosyltransferases (PPRT) are important metabolic enzymes involved in the ribophosphorylation of purine bases and are present in many protozoan parasites. Adenine phosphoribosyltransferase (APRT) and hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) belong to PPRT. APRT and HGXPRT convert adenine, hypoxanthine, guanine, and xanthine into adenosine-5 ′-monophosphate (AMP), inosine-5 ′-monophosphate (IMP), guanosine-5′-monophosphate (GMP), and xanthosine- 5′-monophosphate (XMP), respectively. Purine nucleotides are involved in many functions as components of DNA and RNA, as enzyme cofactors in metabolic pathways, as sources of energy in protozoan parasites. Purine phosphoribosyltransferases are key enzyme in the purine salvage pathway of parasitic protozoa, which is significantly different from the de novo synthesis pathway of the host. In recent years, purine phosphoribosyltransferases have become the interesting research hotspot as an antiparasitic drug candidates target, with major progress in the screening of compounds against protozoan parasites. This review focuses on the basic characteristics, biological functions, inhibitors screening and application of purine phosphoribosyltransferases in parasitic protozoa of Leishmania spp., Trypanosoma spp., Plasmodium spp., and Toxoplasma gondii, so as to provide reference for the research of drug targets and the screening of new inhibitors against parasitic protozoa.
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