...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Structure >dUTPase as a platform for antimalarial drug design: Structural basis for the selectivity of a class of nucleoside inhibitors
【24h】

dUTPase as a platform for antimalarial drug design: Structural basis for the selectivity of a class of nucleoside inhibitors

机译：dUTPase作为抗疟疾药物设计的平台：一类核苷抑制剂选择性的结构基础

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Pyrimidine metabolism is a major route for therapeutic intervention against malaria. Here we report inhibition and structural studies on the deoxyuridine nucleotidohydrolase from the malaria parasite Plasmodium falciparum (PfdUTPase). We have identified a series of triphenylmethane derivatives of deoxyuridine with antimalarial activity in vitro which inhibit specifically the Plasmodium dUTPase versus the human enzyme. A 2.4 Angstrom crystal structure of PfdUTPase in complex with one of these inhibitors reveals an atypical trimeric enzyme in which the triphenyl methane derivative can be seen to select for PfdUTPase by way of interactions between the trityl group and the side chains of residues Phe(46) and Ile(117). Immunofluorescence microscopy studies of parasitized red blood cells reveal that enzyme concentrations are highest during the trophozoite/schizont stages, suggesting that PfdUTPase has a major role in DNA replication. Taken together the data show that PfdUTPase may be considered as an antimalarial drug target.
机译：嘧啶代谢是治疗疟疾的主要途径。在这里，我们报道了疟原虫恶性疟原虫（PfdUTPase）中脱氧尿苷核苷酸水解酶的抑制作用和结构研究。我们已经鉴定出一系列在体外具有抗疟疾活性的脱氧尿苷的三苯基甲烷衍生物，它们相对于人类酶特别抑制疟原虫dUTPase。 PfdUTPase与一种抑制剂形成的2.4埃晶体结构揭示了一种非典型的三聚酶，其中三苯甲基与三苯甲基和残基Phe的侧链之间的相互作用可以看到三苯基甲烷衍生物选择PfdUTPase（46）。和Ile（117）。对寄生红细胞的免疫荧光显微镜研究表明，在滋养体/裂殖体阶段，酶的浓度最高，表明PfdUTPase在DNA复制中起主要作用。数据汇总显示，PfdUTPase可被视为抗疟药物的靶标。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号