HIV-1 reverse transcriptase: structure predictions for the polymerase domain.
Reverse transcriptase (RT) plays an essential role in the life cycle of the human immunodeficiency viruses (HIV). A better understanding of this enzyme, and its two catalytic functions, the DNA polymerase and the RNase H, could lead to the development of new drugs that would specifically block HIV replication. The available genetic, sequence, biochemical, and immunological data on the reverse transcriptase of HIV-1 constrain the possible structure of the DNA polymerase domain. The purpose of this review is to correlate the data and to discuss, in light of that data, a model for the structure of the polymerase domain. In this model, the polymerase domain is approximately 50 to 60 A in diameter with a 20 A opening to accommodate the nucleic acid duplex. The most evolutionarily conserved region of RT (amino acids 20-190 of HIV-1 RT) is proposed to form the inner surface of the 20 A opening to which the nucleic acid hemiduplex is bound.
Laboratory of Mathematical Biology, National Cancer Institute, Bethesda, MD 20892.
A M
AM
Barber
A
A
Hizi
J V
JV
Maizel
S H
SH
Hughes
D000595:Amino Acid Sequence; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry*
D012194:RNA-Directed DNA Polymerase