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逆转录病毒整合体的三维结构

这篇文章第一次报道了一种逆转录病毒整合体(retroviral intasome)的三维结构。

目前,临床上很多用于抑制病毒的药物都是作用在逆转录病毒整合体上。这项研究成果对抗病毒药物的研究,尤其是抗艾滋病药物的研发,具有重要的意义。

文章发表在3月出版的Nature杂志上。

参考文献:Nature. 2010 Mar 11;464(7286):232-6. Epub 2010 Jan 31.

Retroviral intasome assembly and inhibition of DNA strand transfer.
Hare S, Gupta SS, Valkov E, Engelman A, Cherepanov P.

Division of Medicine, Imperial College London, St-Mary's Campus, Norfolk Place, London W2 1PG, UK.

Comment in:

Nature. 2010 Mar 11;464(7286):167-8.

Integrase is an essential retroviral enzyme that binds both termini of linear viral DNA and inserts them into a host cell chromosome. The structure of full-length retroviral integrase, either separately or in complex with DNA, has been lacking. Furthermore, although clinically useful inhibitors of HIV integrase have been developed, their mechanism of action remains speculative. Here we present a crystal structure of full-length integrase from the prototype foamy virus in complex with its cognate DNA. The structure shows the organization of the retroviral intasome comprising an integrase tetramer tightly associated with a pair of viral DNA ends. All three canonical integrase structural domains are involved in extensive protein-DNA and protein-protein interactions. The binding of strand-transfer inhibitors displaces the reactive viral DNA end from the active site, disarming the viral nucleoprotein complex. Our findings define the structural basis of retroviral DNA integration, and will allow modelling of the HIV-1 intasome to aid in the development of antiretroviral drugs.

PMID: 20118915 [PubMed - indexed for MEDLINE]

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    摘要
    目前,临床上很多用于抑制病毒的药物都是作用在逆转录病毒整合体上。这项研究成果对抗病毒药物的研究,尤其是抗艾滋病药物的研发,具有重要的意义。
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    逆转录病毒,三维结构
     
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