Organic chemistry

Base pair

A-DNA

Nucleotide

Polymerase

Biology

Gene

Aptamer

Molecular biology

Reverse transcriptase

Chemistry

Nucleic acid

DNA polymerase

Primer (cosmetics)

Biochemistry

Duplex (building)

Protein Science

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.

Structure of <scp>HIV</scp>‐1 reverse transcriptase bound to a novel 38‐mer hairpin template‐primer <scp>DNA</scp> aptamer

Structure of HIV‐1 reverse transcriptase bound to a novel 38‐mer hairpin template‐primer DNA aptamer