[Studies of the resistance of the human immunodeficiency virus to azidothymidine. I. Kinetic studies of the interaction between reverse transcriptase and a series of its mutant forms with substrates and azidothymidine-5'-trisphosphate].
Prolonged therapy of AIDS patients with azidothymidine results in the development of resistance to the drug. This phenomenon is accompanied by the appearance of point mutations in the pol gene coding for reverse transcriptase (RT). Kinetic studies of interactions of wild type RT and its forms containing the above-mentioned mutations with substrates and azidothymidine 5'-triphosphate have been carried out. Considerable differences in the affinities of RT and the mutants for RNA and DNA heteropolymer templates were established. The mutations did not affect the RT affinity for dNTP; however, its location influenced considerably the inhibition of the reaction with azidothymidine 5'-triphosphate.
Pokholok
D K
DK
Gudima
S O
SO
Esipov
D S
DS
Dobrynin
V N
VN
Memelova
L V
LV
Rechinskiĭ
V O
VO
Kochetkov
S N
SN
D000595:Amino Acid Sequence; D001483:Base Sequence; D004279:DNA, Viral / Q000378:metabolism; D054306:Dideoxynucleotides; D004352:Drug Resistance, Microbial / Q000235:genetics; D015751:Genes, pol; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D017354:Point Mutation; D012367:RNA, Viral / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D013942:Thymine Nucleotides / Q000378:metabolism*; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*
D004279:DNA, Viral; D054306:Dideoxynucleotides; D012367:RNA, Viral; D013942:Thymine Nucleotides; D015215:Zidovudine; C052873:zidovudine triphosphate; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase