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Unraveling the 'DEAD-box' helicases of Plasmodium falciparum

机译:解开恶性疟原虫的“ DEAD-box”解旋酶

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摘要

The causative agent for the most fatal form of malaria, Plasmodium falciparum, has developed insecticide and drug resistance with time. Therefore combating this disease is becoming increasingly difficult and this calls for finding alternate ways to control malaria. One of the feasible ways could be to find out inhibitors/drugs specific for the indispensable enzymes of malaria parasite such as helicases. These helicases, which contain intrinsic nucleic acid-dependent ATPase activity, are capable of enzymatically unwinding energetically stable duplex nucleic acids into single-stranded templates and are required for all the nucleic acid transactions. Most of the helicases contain a set of nine extremely conserved amino acid sequences, which are called 'helicase motifs'. Due to the presence of the DEAD (Asp-Glu-Ala-Asp) in one of the conserved motifs, this family is also known as the 'DEAD-box' family. In this review, using bioinformatic approach, we describe the 'DEAD-box' helicases of malaria parasite R falciparum. An in depth analysis shows that the parasite contains 22 full-length genes, some of which are homologues of well-characterized helicases of this family from other organisms. Recently we have cloned and characterized the first member of this family, which is a homologue of p68 and is expressed during the schizont stage of the development of the parasite [Pradhan, A., Chauhan, V.S., Tuteja, R., 2005a. A novel 'DEAD-box' DNA helicase from Plasmodium falciparum is homologous to p68. Mol. Biochem. Parasitol. 140, 55-60.; Pradhan A., Chauhan VS., Tuteja R., 2005b. Plasmodium falciparum DNA helicase 60 is a schizont stage specific, bipolar and dual helicase stimulated by PKC phosphorylation. Mol. Biochem. Parasitol. 144, 13 3-141.]. It will be really interesting to clone and characterize other members of the 'DEAD-box' family and understand their role in the replication and transmission of the parasite. These detailed studies may help to identify a parasite-specific enzyme, which could be a potential drug target to treat malaria. The various steps at which this probable drug can act are also discussed. (c) 2006 Elsevier B.V. All rights reserved.
机译:疟疾最致命形式的病因是恶性疟原虫,随着时间的推移已发展出杀虫剂和耐药性。因此,与这种疾病作斗争变得越来越困难,这要求寻找控制疟疾的替代方法。可行的方法之一是找出对疟原虫不可或缺的酶(例如解旋酶)具有特异性的抑制剂/药物。这些具有固有的核酸依赖性ATP酶活性的解旋酶能够将能量稳定的双链核酸酶解展开为单链模板,并且是所有核酸交易所必需的。大多数解旋酶包含一组九个极为保守的氨基酸序列,称为“解旋酶基序”。由于在其中一个保守的基序中存在DEAD(Asp-Glu-Ala-Asp),因此该家族也被称为“ DEAD-box”家族。在这篇综述中,我们使用生物信息学方法描述了疟原虫恶性疟原虫的“ DEAD-box”解旋酶。深入分析表明,该寄生虫包含22个全长基因,其中一些是该家族其他生物中特征明确的解旋酶的同源物。最近,我们已经克隆并鉴定了该家族的第一个成员,它是p68的同源物,在寄生虫发育的裂殖体阶段表达[Pradhan,A.,Chauhan,V.S.,Tuteja,R.,2005a。来自恶性疟原虫的新型“ DEAD-box” DNA解旋酶与p68同源。大声笑生化。麻痹醇。 140,55-60。 Pradhan A.,Chauhan VS.,Tuteja R.,2005b。恶性疟原虫DNA解旋酶60是受PKC磷酸化刺激的裂殖体阶段特异性双极性和双重解旋酶。大声笑生化。麻痹醇。 144,13 3-141。]。克隆和表征“ DEAD-box”家族的其他成员并了解它们在寄生虫的复制和传播中的作用将非常有趣。这些详细的研究可能有助于鉴定寄生虫特异性酶,该酶可能是治疗疟疾的潜在药物靶标。还讨论了这种可能的药物可以起作用的各个步骤。 (c)2006 Elsevier B.V.保留所有权利。

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