Abstract
Non-nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase (RT), NNRTIs, which bind to the p66/p51 heterodimeric RT, also interact with the p66/p66 homodimer, whose structure is unknown. (19) F nuclear magnetic resonance of a single 4-trifluoromethylphenylalanine (tfmF) residue, incorporated into the NNRTI binding pocket of the p66/p66 homodimer at position 181, was used to investigate NNRTI binding. In the NNRTI-bound homodimer complex, two different (19) F signals are observed, with the resonance frequencies matching those of the NNRTI-bound p66/p51 heterodimer spectra, in which the individual p66-subunit or p51-subunit were labeled with tfmF at positions 181. These data suggest that the NNRTI-bound p66/p66 homodimer conformation, particularly around residue 181, is very similar to that in the p66/p51 heterodimer, explaining why NNRTI binding to p66/p66 enhances dimer formation.