title: Analysis of mutations at positions 115 and 116 in the dNTP binding site of HIV-1 reverse transcriptase.
abstract: 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.
authors.affiliation: Advanced BioScience Laboratories-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, P. O. Box B, Frederick, MD 21702-1201, USA.
authors.forename: P L
authors.initials: PL
authors.lastname: Boyer
authors.forename: S G
authors.initials: SG
authors.lastname: Sarafianos
authors.forename: E
authors.initials: E
authors.lastname: Arnold
authors.forename: S H
authors.initials: SH
authors.lastname: Hughes
mesh_terms: 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
chemical_list: D003854:Deoxyribonucleotides; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase