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Comparative complement selection in bacteria enables screening for lead compounds targeted to a purine salvage enzyme of parasites.细菌中的比较性补体选择能够筛选出针对寄生虫嘌呤补救酶的先导化合物。
Antimicrob Agents Chemother. 1995 Mar;39(3):620-5. doi: 10.1128/AAC.39.3.620.
2
Expression and properties of recombinant P. falciparum hypoxanthine-guanine phosphoribosyltransferase.
Adv Exp Med Biol. 1998;431:735-9. doi: 10.1007/978-1-4615-5381-6_141.
3
Inactivation of Tritrichomonas foetus and Schistosoma mansoni purine phosphoribosyltransferases by arginine-specific reagents.精氨酸特异性试剂对胎儿三毛滴虫和曼氏血吸虫嘌呤磷酸核糖基转移酶的失活作用。
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Bacterial complementation as a means to test enzyme-ligand interactions.
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Development of a bacterial screen for novel hypoxanthine-guanine phosphoribosyltransferase substrates.用于新型次黄嘌呤-鸟嘌呤磷酸核糖基转移酶底物的细菌筛选方法的开发。
J Mol Microbiol Biotechnol. 2001 Oct;3(4):557-62.
6
High level expression in Escherichia coli of soluble, enzymatically active schistosomal hypoxanthine/guanine phosphoribosyltransferase and trypanosomal ornithine decarboxylase.可溶性、具有酶活性的血吸虫次黄嘌呤/鸟嘌呤磷酸核糖基转移酶和锥虫鸟氨酸脱羧酶在大肠杆菌中的高水平表达。
Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2500-4. doi: 10.1073/pnas.88.6.2500.
7
Altering the purine specificity of hypoxanthine-guanine-xanthine phosphoribosyltransferase from Tritrichomonas foetus by structure-based point mutations in the enzyme protein.通过对酶蛋白进行基于结构的点突变来改变胎儿三毛滴虫次黄嘌呤-鸟嘌呤-黄嘌呤磷酸核糖基转移酶的嘌呤特异性。
Biochemistry. 1998 Nov 24;37(47):16612-9. doi: 10.1021/bi9818974.
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Isolation, sequencing and expression of the gene encoding hypoxanthine-guanine-xanthine phosphoribosyltransferase of Tritrichomonas foetus.胎儿三毛滴虫次黄嘌呤-鸟嘌呤-黄嘌呤磷酸核糖转移酶编码基因的分离、测序及表达
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The role for an invariant aspartic acid in hypoxanthine phosphoribosyltransferases is examined using saturation mutagenesis, functional analysis, and X-ray crystallography.利用饱和诱变、功能分析和X射线晶体学研究了次黄嘌呤磷酸核糖转移酶中不变天冬氨酸的作用。
Biochemistry. 2001 Mar 6;40(9):2754-65. doi: 10.1021/bi001195q.

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Evaluation of the Trypanosoma brucei 6-oxopurine salvage pathway as a potential target for drug discovery.评估布氏锥虫 6-氧嘌呤回收途径作为药物发现的潜在靶点。
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Hypoxanthine phosphoribosyltransferase from Trypanosoma cruzi as a target for structure-based inhibitor design: crystallization and inhibition studies with purine analogs.克氏锥虫次黄嘌呤磷酸核糖转移酶作为基于结构的抑制剂设计靶点：嘌呤类似物的结晶与抑制研究
Antimicrob Agents Chemother. 1997 Aug;41(8):1686-92. doi: 10.1128/AAC.41.8.1686.

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The crystal structure of human hypoxanthine-guanine phosphoribosyltransferase with bound GMP.结合GMP的人次黄嘌呤-鸟嘌呤磷酸核糖转移酶的晶体结构。
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Isolation, sequencing and expression of the gene encoding hypoxanthine-guanine-xanthine phosphoribosyltransferase of Tritrichomonas foetus.胎儿三毛滴虫次黄嘌呤-鸟嘌呤-黄嘌呤磷酸核糖转移酶编码基因的分离、测序及表达
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Human hypoxanthine-guanine phosphoribosyltransferase. Complete amino acid sequence of the erythrocyte enzyme.人次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶。红细胞酶的完整氨基酸序列。
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Purine salvage by Tritrichomonas foetus.胎儿三毛滴虫的嘌呤补救途径
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Purine salvage networks in Giardia lamblia.蓝氏贾第鞭毛虫中的嘌呤补救网络。
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Purine metabolism in the schistosomes: potential targets for chemotherapy.
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Isolation and characterization of a full-length expressible cDNA for human hypoxanthine phosphoribosyl transferase.人次黄嘌呤磷酸核糖基转移酶全长可表达cDNA的分离与鉴定
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Purine metabolism in Trypanosoma cruzi.克氏锥虫中的嘌呤代谢
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Human hypoxanthine phosphoribosyltransferase. I. Purification, properties, and specificity.人次黄嘌呤磷酸核糖基转移酶。I. 纯化、性质及特异性
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Purine and pyrimidine synthesis by the avian malaria parasite, Plasmodium lophurae.禽类疟原虫——洛氏疟原虫的嘌呤和嘧啶合成
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细菌中的比较性补体选择能够筛选出针对寄生虫嘌呤补救酶的先导化合物。

Comparative complement selection in bacteria enables screening for lead compounds targeted to a purine salvage enzyme of parasites.

作者信息

Eakin A E, Nieves-Alicea R, Tosado-Acevedo R, Chin M S, Wang C C, Craig S P

机构信息

Department of Biochemistry, University of Puerto Rico School of Medicine, San Juan 00936-5067, USA.

出版信息

Antimicrob Agents Chemother. 1995 Mar;39(3):620-5. doi: 10.1128/AAC.39.3.620.

DOI:10.1128/AAC.39.3.620
PMID:7793862
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC162594/
Abstract

Expression plasmids encoding the hypoxanthine phosphoribosyltransferases (HPRTs) of Plasmodium falciparum, Schistosoma mansoni, Tritrichomonas foetus, and Homo sapiens were subcloned into genetically deficient Escherichia coli that requires complementation by the activity of a recombinant HPRT for growth on semidefined medium. Fifty-nine purine analogs were screened for their abilities to inhibit the growth of these bacteria. Several compounds that selectively altered the growth of the bacteria complemented by the malarial, schistosomal, or tritrichomonal HPRT compared with the growth of bacteria expressing the human enzyme were identified. These results demonstrate that the recombinant approach to screening compounds by complement selection in a comparative manner provides a rapid and efficient method for the identification of new lead compounds selectively targeted to the purine salvage enzymes of parasites.

摘要

编码恶性疟原虫、曼氏血吸虫、胎儿三毛滴虫和人类次黄嘌呤磷酸核糖转移酶（HPRTs）的表达质粒被亚克隆到基因缺陷型大肠杆菌中，该大肠杆菌需要重组HPRT的活性进行互补才能在半限定培养基上生长。对59种嘌呤类似物抑制这些细菌生长的能力进行了筛选。与表达人类酶的细菌生长相比，鉴定出几种化合物能选择性地改变由疟疾、血吸虫或三毛滴虫HPRT互补的细菌的生长。这些结果表明，以比较方式通过互补选择筛选化合物的重组方法为鉴定选择性靶向寄生虫嘌呤补救酶的新先导化合物提供了一种快速有效的方法。