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恶性疟原虫特异性解旋酶 2 是一种双极解旋酶,对寄生虫的生长至关重要。

Plasmodium falciparum specific helicase 2 is a dual, bipolar helicase and is crucial for parasite growth.

机构信息

Parasite Biology Group, ICGEB, P. O. Box 10504, Aruna Asaf Ali Marg, New Delhi, 110067, India.

出版信息

Sci Rep. 2019 Feb 6;9(1):1519. doi: 10.1038/s41598-018-38032-1.

DOI:10.1038/s41598-018-38032-1
PMID:30728406
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6365506/
Abstract

Human malaria infection is a major challenge across the globe and is responsible for millions of deaths annually. Rapidly emerging drug resistant strains against the new class of anti-malarial drugs are major threat to control the disease burden worldwide. Helicases are present in every organism and have important role in various nucleic acid metabolic processes. Previously we have reported the presence of three parasite specific helicases (PSH) in Plasmodium falciparum 3D7 strain. Here we present the detailed biochemical characterization of PfPSH2. PfPSH2 is DNA and RNA stimulated ATPase and is able to unwind partially duplex DNA and RNA substrates. It can translocate in both 3' to 5' and 5' to 3' directions. PfPSH2 is expressed in all the stages of intraerythrocytic development and it is localized in cytoplasm in P. falciparum 3D7 strain. The dsRNA mediated inhibition study suggests that PfPSH2 is important for the growth and survival of the parasite. This study presents the detailed characterization of PfPSH2 and lays the foundation for future development of PfPSH2 as drug target.

摘要

人类疟疾感染是全球范围内的一个主要挑战,每年导致数百万人死亡。新的抗疟药物类别中迅速出现的耐药菌株是全球控制疾病负担的主要威胁。解旋酶存在于每个生物体中,在各种核酸代谢过程中发挥着重要作用。我们之前曾报道过恶性疟原虫 3D7 株中有三种寄生虫特异性解旋酶(PSH)。在这里,我们详细介绍 PfPSH2 的生化特性。PfPSH2 是 DNA 和 RNA 刺激的 ATP 酶,能够解旋部分双链 DNA 和 RNA 底物。它可以在 3' 到 5' 和 5' 到 3' 方向移动。PfPSH2 在红细胞内发育的所有阶段都有表达,在恶性疟原虫 3D7 株中定位于细胞质。dsRNA 介导的抑制研究表明 PfPSH2 对寄生虫的生长和存活很重要。这项研究详细描述了 PfPSH2 的特性,并为未来将 PfPSH2 作为药物靶点的开发奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47d4/6365506/adf5c105d066/41598_2018_38032_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47d4/6365506/7cf64ce0c026/41598_2018_38032_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47d4/6365506/518d762ff726/41598_2018_38032_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47d4/6365506/bd9de49e0fc3/41598_2018_38032_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47d4/6365506/bf57e7ab9431/41598_2018_38032_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47d4/6365506/bea6ed7c03d3/41598_2018_38032_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47d4/6365506/db6125b54eab/41598_2018_38032_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47d4/6365506/708b81dd43f8/41598_2018_38032_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47d4/6365506/adf5c105d066/41598_2018_38032_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47d4/6365506/7cf64ce0c026/41598_2018_38032_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47d4/6365506/518d762ff726/41598_2018_38032_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47d4/6365506/bd9de49e0fc3/41598_2018_38032_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47d4/6365506/bf57e7ab9431/41598_2018_38032_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47d4/6365506/bea6ed7c03d3/41598_2018_38032_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47d4/6365506/db6125b54eab/41598_2018_38032_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47d4/6365506/708b81dd43f8/41598_2018_38032_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47d4/6365506/adf5c105d066/41598_2018_38032_Fig8_HTML.jpg

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本文引用的文献

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