5D3G

Structure of HIV-1 Reverse Transcriptase Bound to a Novel 38-mer Hairpin Template-Primer DNA Aptamer

Summary for 5D3G

• Entry DOI: 10.2210/pdb5d3g/pdb
• Related PRD ID: PRD_900003
• Descriptor: HIV-1 REVERSE TRANSCRIPTASE P66 subunit, HIV-1 REVERSE TRANSCRIPTASE P51 subunit, DNA aptamer (38-MER), ... (7 entities in total)
• Functional Keywords: reverse transcriptase, hiv, dna aptamer, 2-o-methylcytidine, p66, p51, transferase
• Biological source: Human immunodeficiency virus type 1 group M subtype B (isolate BH10) (HIV-1); More
• Total number of polymer chains: 6
• Total formula weight: 256994.30

Authors

Miller, M.T.,Tuske, S.,Das, K.,Arnold, E. (deposition date: 2015-08-06, release date: 2015-09-30, Last modification date: 2023-09-27)

Primary citation

Miller, M.T.,Tuske, S.,Das, K.,DeStefano, J.J.,Arnold, E.
Structure of HIV-1 reverse transcriptase bound to a novel 38-mer hairpin template-primer DNA aptamer.
Protein Sci., 25:46-55, 2016

PubMed Abstract: 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 Å 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.

PubMed: 26296781
DOI: 10.1002/pro.2776

Experimental method

X-RAY DIFFRACTION (2.3 Å)