Enzymatic properties and sensitivity to inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase with Glu-138-->Arg and Tyr-188-->His mutations.

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

Enzymatic properties and sensitivity to inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase with Glu-138-->Arg and Tyr-188-->His mutations.

Antiviral Res. 1994 May;24(1):43-57. Unique Identifier : AIDSLINE MED/95030978
Zhang H; Vrang L; Backbro K; Unge T; Noreen R; Oberg B; Medivir AB, Huddinge, Sweden.

Abstract: Two mutants of HIV-1 reverse transcriptase (RT), Tyr-188-->His and Glu-138-->Arg have been prepared and their catalytic properties and sensitivities to inhibitors studied. As compared to wild type RT, a reduction in catalytic efficiency and turn over number was observed, especially for the Tyr-188-->His mutant. The non-nucleoside inhibitors nevirapine, L-697,661 and 9-Cl-TIBO caused a mixed type of inhibition of RT (Arg-138) with respect to substrate, and with the exception of a non-competitive inhibition by nevirapine, also a mixed type of inhibition of RT (His-188). Foscarnet (PFA) caused a non-competitive type of inhibition of RT (Arg-138) and a mixed inhibition of RT (His-188). The inhibition by ddG-TP was competitive with both mutant RTs. Inhibition by nevirapine gave IC50 values of 0.15, 0.23 and 0.72 microM; by 9-Cl-TIBO of 0.20, 2.50 and 10.3 microM; by L-697,661 of 0.064, 0.28 and 0.60 microM; by ddGTP of 0.13, 0.14 and 0.02 microM; by PFA of 17.0, 48.0 and 15.0 microM for RT wt, RT (Arg-138) and RT (His-188), respectively.

Keywords: Amino Acids/*GENETICS Antiviral Agents/*PHARMACOLOGY Base Sequence Benzodiazepines/PHARMACOLOGY Benzoxazoles/PHARMACOLOGY Binding, Competitive Comparative Study Deoxyguanine Nucleotides/PHARMACOLOGY Foscarnet/PHARMACOLOGY Human Imidazoles/PHARMACOLOGY Kinetics Molecular Sequence Data *Mutation Pyridines/PHARMACOLOGY Pyridones/PHARMACOLOGY RNA-Directed DNA Polymerase/*ANTAGONISTS & INHIB/*GENETICS Sensitivity and Specificity Support, Non-U.S. Gov't JOURNAL ARTICLE
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M9510018

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