Biochemical mechanism of human immunodeficiency virus type 1 reverse transcriptase resistance to stavudine.
We have found a close correlation between viral stavudine (d4T) resistance and resistance to d4T-triphosphate at the human immunodeficiency virus type 1 reverse transcriptase (RT) level. RT from site-directed mutants with 69S-XX codon insertions and/or conventional zidovudine resistance mutations seems to be involved in an ATP-dependent resistance mechanism analogous to pyrophosphorolysis, whereas the mechanism for RT with the Q151M or V75T mutation appears to be independent of added ATP for reducing binding to d4T-triphosphate.
Lennerstrand
J
J
Virco UK, Ltd, Cambridge CB4 0GA, United Kingdom. johan.lennerstrand@impi.ki.se
Stammers
D K
DK
Larder
B A
BA
D000255:Adenosine Triphosphate / Q000378:metabolism*; D019943:Amino Acid Substitution; D001665:Binding Sites; D004352:Drug Resistance, Microbial / Q000502:physiology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D018119:Stavudine / Q000378:metabolism / Q000494:pharmacology*
D018894:Reverse Transcriptase Inhibitors; D000255:Adenosine Triphosphate; D018119:Stavudine; D054303:HIV Reverse Transcriptase