Interaction of HIV-1 reverse transcriptase with modified oligonucleotide primers containing 2'-O-beta-D-ribofuranosyladenosine.
Modified synthetic oligodeoxyribonucleotides containing 2'-O-beta-D-ribofuranosyladenosine were used as primers in the RNA-dependent DNA synthesis catalyzed by HIV-1 reverse transcriptase. The degree of elongation of the primers depends on the position of the additional ribose unit, its presence in the specific position of the primer (-4) (and only in it) completely preventing elongation. Computer-modeled binding of the modified primers to the active site of reverse transcriptase demonstrated that steric hindrances arising from the interaction of the additional ribose residue with the reverse transcriptase region 262-270 interacting with the minor groove of the DNA substrate prevents elongation in the above mentioned case.
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia.
A S
AS
Golubeva
B S
BS
Ermolinsky
E V
EV
Efimtseva
V L
VL
Tunitskaya
A
A
van Aerschot
P
P
Herdewijn
S N
SN
Mikhailov
S N
SN
Kochetkov
D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D017931:DNA Primers / Q000737:chemistry* / Q000378:metabolism; D004261:DNA Replication; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D008956:Models, Chemical; D011485:Protein Binding; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D014779:Virus Replication
D017931:DNA Primers; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D000241:Adenosine