Analysis of amino insertion mutations in the fingers subdomain of HIV-1 reverse transcriptase. 1999

P L Boyer, and J Lisziewicz, and F Lori, and S H Hughes
ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, MD, 21702-1201, USA.

In response to dideoxy inosine/hydroxyurea dual therapy, HIV-1 (human immunodeficiency virus type-1) variants were isolated that had a small amino acid insertion and flanking amino acid substitutions in the fingers subdomain of HIV-1. We have analyzed the reverse transcriptase variants for their effects on HIV-1 reverse transcriptase activity. The data suggests that the inserted amino acid residues are responsible for low-level resistance to the nucleoside analog ddITP, while the role of the flanking amino acid substitutions is to compensate for the deleterious effects of the insertion.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D003838 Deoxyadenine Nucleotides Adenine nucleotides which contain deoxyribose as the sugar moiety. Deoxyadenosine Phosphates,Nucleotides, Deoxyadenine,Phosphates, Deoxyadenosine
D004352 Drug Resistance, Microbial The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS). Antibiotic Resistance,Antibiotic Resistance, Microbial,Antimicrobial Resistance, Drug,Antimicrobial Drug Resistance,Antimicrobial Drug Resistances,Antimicrobial Resistances, Drug,Drug Antimicrobial Resistance,Drug Antimicrobial Resistances,Drug Resistances, Microbial,Resistance, Antibiotic,Resistance, Drug Antimicrobial,Resistances, Drug Antimicrobial
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D015658 HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS). HTLV-III Infections,HTLV-III-LAV Infections,T-Lymphotropic Virus Type III Infections, Human,HIV Coinfection,Coinfection, HIV,Coinfections, HIV,HIV Coinfections,HIV Infection,HTLV III Infections,HTLV III LAV Infections,HTLV-III Infection,HTLV-III-LAV Infection,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,T Lymphotropic Virus Type III Infections, Human
D016049 Didanosine A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite. 2',3'-Dideoxyinosine,Dideoxyinosine,ddI (Antiviral),NSC-612049,Videx,2',3' Dideoxyinosine,NSC 612049,NSC612049
D016254 Mutagenesis, Insertional Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene or extragenic sequence. This may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. Proviral DNA insertions into or adjacent to a cellular proto-oncogene can interrupt GENETIC TRANSLATION of the coding sequences or interfere with recognition of regulatory elements and cause unregulated expression of the proto-oncogene resulting in tumor formation. Gene Insertion,Insertion Mutation,Insertional Activation,Insertional Mutagenesis,Linker-Insertion Mutagenesis,Mutagenesis, Cassette,Sequence Insertion,Viral Insertional Mutagenesis,Activation, Insertional,Activations, Insertional,Cassette Mutagenesis,Gene Insertions,Insertion Mutations,Insertion, Gene,Insertion, Sequence,Insertional Activations,Insertional Mutagenesis, Viral,Insertions, Gene,Insertions, Sequence,Linker Insertion Mutagenesis,Mutagenesis, Linker-Insertion,Mutagenesis, Viral Insertional,Mutation, Insertion,Mutations, Insertion,Sequence Insertions
D054303 HIV Reverse Transcriptase A reverse transcriptase encoded by the POL GENE of HIV. It is a heterodimer of 66 kDa and 51 kDa subunits that are derived from a common precursor protein. The heterodimer also includes an RNAse H activity (RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS) that plays an essential role the viral replication process. Reverse Transcriptase, HIV,Reverse Transcriptase, Human Immunodeficiency Virus,Transcriptase, HIV Reverse

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