Nucleotide Sugar Pucker Preference Mitigates Excision by HIV-1 RT

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• 作者：Ken Yamada ; Alexander S. Wahba ; Jean A. Bernatchez ; Tatiana Ilina ; Sa煤l Mart铆nez-Montero ; Maryam Habibian ; Glen F. Deleavey ; Matthias G枚tte ; Michael A. Parniak ; Masad J. Damha
• 刊名：ACS Chemical Biology
• 出版年：2015
• 出版时间：September 18, 2015
• 年：2015
• 卷：10
• 期：9
• 页码：2024-2033
• 全文大小：665K
• ISSN：1554-8937

文摘

A series of DNA primers containing nucleotides with various sugar pucker conformations at the 3鈥?terminus were chemically synthesized by solid-phase synthesis. The ability of wild-type (WT) HIV-1 reverse transcriptase (RT) and AZT-resistant (AZTr) RT to excise the 3鈥?terminal nucleotide was assessed. Nucleosides with a preference for the North conformation were more refractory to excision by both WT-RT and AZTr-RT. We found that DNA primers that contain North puckered-nucleotides at the 3鈥?terminus can also affect the translocation status of the RT/template/primer complex, which provides an underlying mechanism to avoid being excised. Together, these results point to a correlation between the sugar conformation of the 3鈥?terminal nucleotide, the precise position of HIV-1 RT on its nucleic acid substrate, and, in turn, its catalytic function. Nucleotide sugar conformation is therefore an important parameter in defining the susceptibility to RT-catalyzed phosphorolytic excision.