HIV reverse transcriptase structure-function relationships.
HIV reverse transcriptase (RT) is the target of the most widely used treatments for AIDS. Biochemical and mutagenesis studies performed on HIV-1 RT are reviewed in light of the enzyme's structure and functions. Features described include domain arrangement, dimerization, proteolytic processing, and specific recognition of the priming tRNA. Possible regions of functional importance as determined by comparative amino acid sequence analysis and by site-directed mutagenesis are identified. Among the conclusions of the analysis is the unexpected realization that the substrate for proteolytic maturation of the HIV-1 RT p66/p66 homodimer to the p66/p51 heterodimer is most likely an unfolded RNase H domain. In addition, the current progress in crystallization and structure determination of HIV-1 RT is described. Finally, a functional-model of the active reverse transcription complex is presented.
Jacobo-Molina
A
A
Center for Advanced Biotechnology and Medicine (CABM), Rutgers University, Piscataway, New Jersey 08854-5638.
Arnold
E
E
D000595:Amino Acid Sequence; D001665:Binding Sites; D004722:Endoribonucleases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006678:HIV / Q000201:enzymology*; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012194:RNA-Directed DNA Polymerase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016914:Ribonuclease H; D012689:Sequence Homology, Nucleic Acid; D014961:X-Ray Diffraction
D046911:Macromolecular Substances; D012194:RNA-Directed DNA Polymerase; D004722:Endoribonucleases; D016914:Ribonuclease H