Figure 4.  Models showing the binding of ATP and PPi to AZT-resistant HIV-1 RT.  van der Waals surfaces are drawn for polymerase active site residues (magenta) and residues involved in ATP binding and AZT resistance (yellow).  Mutated amino acids M41L, K70R, L210W, and T215Y are shown with black labels, and amino acids that could be involved with ATP binding but that are not mutated (E44, K46) are shown with magenta labels.  The two terminal nucleotide base pairs of the template-primer are shown.  The 3' end of the primer is AZTMP; the azido group is labeled.  The amino acid substitution T215Y has been modeled here in order to show potential aromatic interactions with this residue.  The wild-type amino acids at K219 and D67 were retained in the figure to show a potential salt bridge between the residues.  The AZT resistance mutations at these residues will destroy this salt bridge and may increase the ability of the pyrophosphate donor to bind.  K219 and D67 are shown as stick diagrams to avoid obscuring the pyrophosphate binding site.  The presumptive salt bridge between Lys219 and Asp67 is shown as a dotted line.  Panel A shows the model with PPi bound, and panel B shows the model with ATP bound.