Characterization of the binding site for nevirapine (BI-RG-587), a nonnucleoside inhibitor of human immunodeficiency virus type-1 reverse transcriptase.
Nevirapine (BI-RG-587) is a potent and specific non-nucleoside inhibitor of human immunodeficiency virus type-1 reverse transcriptase. The compound is non-competitive with respect to template, primer, and nucleoside triphosphates indicating that BI-RG-587 does not act directly at the catalytic site. The binding site for this inhibitor was investigated by employing an azido photoaffinity analogue, BI-RJ-70, to covalently label the enzyme. The resulting photoadduct was subjected to enzymatic digestion by trypsin and endoproteinase lys-C and a single, highly labeled peptide was identified as residues 174-199. Sequencing of this peptide identified Tyr-181 and Tyr-188 as labeled residues.
Cohen
K A
KA
Department of Analytical Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut 06877.
Hopkins
J
J
Ingraham
R H
RH
Pargellis
C
C
Wu
J C
JC
Palladino
D E
DE
Kinkade
P
P
Warren
T C
TC
Rogers
S
S
Adams
J
J
D000345:Affinity Labels; D000595:Amino Acid Sequence; D001381:Azepines / Q000378:metabolism*; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D015497:HIV-1 / Q000201:enzymology*; D008969:Molecular Sequence Data; D019829:Nevirapine; D010449:Peptide Mapping; D011725:Pyridines / Q000378:metabolism*; D018894:Reverse Transcriptase Inhibitors; D014357:Trypsin
D000345:Affinity Labels; D001381:Azepines; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D014357:Trypsin