Crystal structure of HIV-1 reverse transcriptase bound to a nucleotide-competitive reverse transcriptase inhibitor and the use thereof

The present invention relates to a co-crystal comprising a HIV-1 reverse transcriptase (RT) polypeptide and a nucleotide competing reverse transcriptase inhibitor (NcRTI). In particular, the HIV-1 reverse transcriptase polypeptide comprises a ligand binding pocket (LBP) in a hinge region at the interface between a p66 thumb domain defined by residues 1 to 84 and 120 to 150 in the p66 subunit of SEQ ID No. 1 and palm domains defined by residues 85 to 119 and 151 to 242 in the p66 subunit of SEQ ID No. 1, in the vicinity of the polymerase active site defined by residues 110, 185 and 186 of SEQ ID No. 1 and close to the ATP binding site of the RT.