Analysis of mutations at positions 115 and 116 in the dNTP binding site of HIV-1 reverse transcriptase.
We have examined amino acid substitutions at residues 115 and 116 in the reverse transcriptase (RT) of HIV-1. A number of properties were examined, including polymerization and processivity on both DNA and RNA templates, strand displacement, ribonucleotide misincorporation, and resistance to nucleoside analogs. The RT variants Tyr-115-Phe and Phe-116-Tyr are similar to wild-type HIV-1 RT in most, but not all, respects. In contrast, the RT variant Tyr-115-Val is significantly impaired in polymerase activity compared with wild-type RT; however, Tyr-115-Val is able to incorporate ribonucleotides as well as deoxyribonucleotides during polymerization and is resistant to a variety of nucleoside analogs.
Boyer
P L
PL
Advanced BioScience Laboratories-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, P. O. Box B, Frederick, MD 21702-1201, USA.
Sarafianos
S G
SG
Arnold
E
E
Hughes
S H
SH
D001665:Binding Sites; D003854:Deoxyribonucleotides / Q000235:genetics / Q000378:metabolism*; D004352:Drug Resistance, Microbial; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D007700:Kinetics; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology
D003854:Deoxyribonucleotides; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase