| Autor: |
Steve Tuske, Kalyan Das, Matthew T. Miller, Jeffrey J. DeStefano, Eddy Arnold |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
Protein Science. 25:46-55 |
| ISSN: |
0961-8368 |
| DOI: |
10.1002/pro.2776 |
| Popis: |
The development of a modified DNA aptamer that binds HIV-1 reverse transcriptase (RT) with ultra-high affinity has enabled the X-ray structure determination of an HIV-1 RT-DNA complex to 2.3 A resolution without the need for an antibody Fab fragment or RT-DNA cross-linking. The 38-mer hairpin-DNA aptamer has a 15 base-pair duplex, a three-deoxythymidine hairpin loop, and a five-nucleotide 5'-overhang. The aptamer binds RT in a template-primer configuration with the 3'-end positioned at the polymerase active site and has 2'-O-methyl modifications at the second and fourth duplex template nucleotides that interact with the p66 fingers and palm subdomains. This structure represents the highest resolution RT-nucleic acid structure to date. The RT-aptamer complex is catalytically active and can serve as a platform for studying fundamental RT mechanisms and for development of anti-HIV inhibitors through fragment screening and other approaches. Additionally, the structure allows for a detailed look at a unique aptamer design and provides the molecular basis for its remarkably high affinity for RT. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
Plný text