RESISTANCE TO NEVIRAPINE OF HIV-1 REVERSE TRANSCRIPTASE MUTANTS - LOSS OF STABILIZING INTERACTIONS AND THERMODYNAMIC OR STERIC BARRIERS ARE INDUCED BY DIFFERENT SINGLE AMINO ACID SUBSTITUTIONS

摘要

The kinetic parameters governing the inhibition by Nevirapine of the RNA-dependent DNA synthesis catalyzed by HIV-1 reverse transcriptase have been determined by steady-state kinetic analysis with the wild-type enzyme and with mutant reverse transcriptases containing the single amino acid substitutions L100I, K103N, V106A, V179D, Y181I and Y188L. While the mutant V179D was inhibited by Nevirapine as the wild-type enzyme, all the other mutations displayed a 17 to 90-fold reduced sensitivity to the drug in the order: Y181I < (i.e. less sensitive) Y188L < V106A