Mechanism of inhibition of HIV-1 reverse transcriptase by nonnucleoside inhibitors
RA Spence, WM Kati, KS Anderson, KA Johnson - Science, 1995 - science.org
The mechanism of inhibition of HIV-1 reverse transcriptase by three nonnucleoside
inhibitors is described. Nevirapine, O-TIBO, and CI-TIBO each bind to a hydrophobic pocket
in the enzyme-DNA complex close to the active site catalytic residues. Pre-steady-state
kinetic analysis was used to establish the mechanism of inhibition by these noncompetitive
inhibitors. Analysis of the pre-steady-state burst of DNA polymerization indicated that
inhibitors blocked the chemical reaction, but did not interfere with nucleotide binding or the …
inhibitors is described. Nevirapine, O-TIBO, and CI-TIBO each bind to a hydrophobic pocket
in the enzyme-DNA complex close to the active site catalytic residues. Pre-steady-state
kinetic analysis was used to establish the mechanism of inhibition by these noncompetitive
inhibitors. Analysis of the pre-steady-state burst of DNA polymerization indicated that
inhibitors blocked the chemical reaction, but did not interfere with nucleotide binding or the …
Mechanism of inhibition of HIV-1 reverse transcriptase by non-nucleoside inhibitors
The structure of unliganded HIV-1 reverse transcriptase has been determined at 2.35 Å
resolution and refined to an R-factor of 0.219 (for all data) with good stereochemistry. The
unliganded structure was produced by soaking out a weak binding non-nucleoside inhibitor,
HEPT, from pregrown crystals. Comparison with the structures of four different RT and non-
nucleoside inhibitor complexes reveals that only minor domain rearrangements occur, but
there is a significant repositioning of a three-stranded β-sheet in the p66 subunit (containing …
resolution and refined to an R-factor of 0.219 (for all data) with good stereochemistry. The
unliganded structure was produced by soaking out a weak binding non-nucleoside inhibitor,
HEPT, from pregrown crystals. Comparison with the structures of four different RT and non-
nucleoside inhibitor complexes reveals that only minor domain rearrangements occur, but
there is a significant repositioning of a three-stranded β-sheet in the p66 subunit (containing …