Figure 1

Interaction between residue N348 in the p51 subunit of HIV-1 RT and the RNA template. A) Crystal structure of HIV-1 RT in complex with a polypurine tract RNA/DNA T/P (pdb accession code 1HYS). The p66 DNA polymerase, connection and RNase H domains are colored cyan, green and yellow, respectively. The p51 subunit is colored orange. The DNA and RNA strands are colored white and purple, respectively. Residues in the connection and RNase H domain that form part of the nucleic acid binding tract are shown in spacefill (and colored according to domain color). B) Location of the β14-β15 loop in the p51 subunit of HIV-1 RT in complex with a PPT RNA/DNA hybrid. Residues 345 and 346 reside > 7Å from the RNA strand. C) Location of the β14-β15 in the p51 subunit of HIV-1 RT in complex with an RNA/DNA duplex that extends into the RNase H active site. Residues 345 and 346 all directly contact the RNA template. The co-ordinates for the model were kindly provided by Dr M. Nowotny. D, E, F) Impact of the N348I (D), N348A (E) and N348L (F) mutations on the β14-β15 loop in the p51 subunit of HIV-1 RT in complex with an RNA/DNA duplex that extends into the RNase H active site. The WT and mutant structures are colored green and pink, respectively. The co-ordinates for this structure were kindly provided by Dr M. Nowotny (NIDDK, NIH). Mutations were introduced into this structure using MOE. Charges were calculated using the Gasteiger method, and iterative minimizations were carried out using the AMBER 99 force field until the energy difference between iterations was less than 0.0001 kcal/mol per Å.