恰加斯利什曼原虫DNA拓扑异构酶II的特性：一个潜在的化疗靶点。
Characterization of Leishmania chagasi DNA topoisomerase II: a potential chemotherapeutic target.
作者信息
De Sousa Jacira M A, Lareau Susan M, Pearson Richard D, Carvalho Edgar M, Mann Barbara J, Jeronimo Selma M B
机构信息
Department of Biochemistry, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
出版信息
Scand J Infect Dis. 2003;35(11-12):826-9. doi: 10.1080/00365540310017023.
DNA topoisomerase II (topo II), an enzyme essential for cellular replication, is an eminent target for antimicrobial therapy against Leishmania chagasi, the major cause of visceral leishmaniasis in Latin America. The complete L. chagasi (Lch) TOP2 gene, encoding L. chagasi topo II, was isolated from genomic DNA using the polymerase chain reaction. The LchTOP2 gene revealed an open reading frame (ORF) of 3,711 base pairs predicting a protein with 1,236 amino acids and an estimated molecular weight of 140 kDA. The L. chagasi topo II sequence had high identity with the L. donovani topo II (98.8%) and L. infantum topo II (98.7%), followed by Crithidia fasciculata topo II (84.4%), Trypanosoma cruzi topo II (67.6%) and Trypanosoma brucei topo II (66.6%). Lch topo II had low identity with the human homologs htopo II alpha (26.3%) and htopo II beta (26.4%). Differences between L. chagasi TOP2 and human TOP2 genes suggest that leishmanial topo II is a potential target for the development of new antileishmanial agents.
DNA拓扑异构酶II（拓扑异构酶II）是细胞复制所必需的一种酶，是针对拉丁美洲内脏利什曼病的主要病原体恰加斯利什曼原虫进行抗菌治疗的一个重要靶点。使用聚合酶链反应从基因组DNA中分离出了编码恰加斯利什曼原虫拓扑异构酶II的完整恰加斯利什曼原虫（Lch）TOP2基因。LchTOP2基因显示出一个3711个碱基对的开放阅读框（ORF），预测编码一个含有1236个氨基酸、估计分子量为140 kDa的蛋白质。恰加斯利什曼原虫拓扑异构酶II序列与杜氏利什曼原虫拓扑异构酶II（98.8%）和婴儿利什曼原虫拓扑异构酶II（98.7%）具有高度同一性，其次是克氏锥虫拓扑异构酶II（84.4%）、克氏锥虫拓扑异构酶II（67.6%）和布氏锥虫拓扑异构酶II（66.6%）。Lch拓扑异构酶II与人类同源物htopo II alpha（26.3%）和htopo II beta（26.4%）的同一性较低。恰加斯利什曼原虫TOP2基因与人类TOP2基因之间的差异表明，利什曼原虫拓扑异构酶II是开发新型抗利什曼原虫药物的一个潜在靶点。
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