STRUCTURE OF HIV-1 RT TIBO R-86183 COMPLEX REVEALS SIMILARITY IN THE BINDING OF DIVERSE NONNUCLEOSIDE INHIBITORS/

We report the structure of HIV-I reverse transcriptase (RT) complexed with the nonnucleoside inhibitor TIBO R 86183 at 3.0 Angstrom resoluti on. Comparing this structure with those of complexes of HIV-1 RT/alpha -APA R 95845 and HIV-1 RT/nevirapine provides a basis for understandin g the nature of nonnucleoside inhibitor binding, the structure of the binding site and the interactions between the bound inhibitors and sur rounding amino acid residues as well as for understanding mechanisms o f inhibition by and resistance to nonnucleoside inhibitors. Ail three inhibitors considered assume a similar butterfly-like shape and bind t o HIV-1 RT in a very similar way. important differences occur in the c onformation of amino acid residues that form the binding pocket.