Locations of the drug-resistance mutations in HIV-1 RT.  On the right is a structure of HIV-1 RT bound to double-stranded DNA.  The locations of the dNTP binding site and the NNRTI binding site are shown as space-filling models; the NRTI binding site is shown in gold, the NNRTI binding site is shown in blue.  The DNA is shown as a ribbon, the template strand is black, and the primer strand is purple.  The RNase H active site amino acids are shown in red.  The subdomains of p66 are shown in the following colors: fingers, blue; palm, red; thumb, green; connection, yellow.   The RNase H domain is orange; p51 is gray.  The sites of the mutations that lead to resistance to NRTIs and NNRTIs are shown on the left.  The structure is shown with an NNRTI (TIBO) bound; TIBO is shown in green.  The sites of mutations that confer resistance to NNRTIs are shown in blue; these sites surround the NNRTI binding pocket.  The active site amino acids are shown in red and labeled (D110, D185, D186).  Some of the NRTI resistance mutations are relatively far from the dNTP binding site.  The sites where NRTI resistance mutations arise in the beta3-beta4 loop of the fingers (K65, D67, T69, K70) move closer to the active site when a dNTP is bound and the fingers close down on the bound dNTP (see Polymerization Reaction).