title: A possible role for cysteine residues in the fidelity of DNA synthesis exhibited by the reverse transcriptases of human immunodeficiency viruses type 1 and type 2.
abstract: HIV reverse transcriptases (RTs) have few cysteine residues relative to other RTs and retain their DNA polymerization functions following chemical modification by thiol-specific reagents. The functional role of the cysteines in the fidelity of the DNA-dependent DNA synthesis of HIV RTs has been addressed by chemical modification of the wild-type enzymes in combination with the analysis of an enzymatically active mutant HIV-1 RT in which all cysteines were modified to serines. We have observed an increase in 3'-terminal mispair extension efficiency exhibited by chemically modified HIV-1 and HIV-2 RTs. The possible involvement of cysteine residues was further substantiated using the cysteine-free mutant HIV-1 RT that displays an increased efficiency of mispair extension. These results provide evidence for a possible role of cysteine residues in the fidelity of DNA synthesis catalyzed by HIV RTs.
authors.affiliation: Department of Cell Biology and Histology, Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Bakhanashvili
authors.forename: A
authors.initials: A
authors.lastname: Hizi
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D003545:Cysteine / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000096:biosynthesis*; D006678:HIV / Q000201:enzymology*; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000201:enzymology; D015498:HIV-2 / Q000201:enzymology; D008969:Molecular Sequence Data; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D004279:DNA, Viral; C072416:reverse transcriptase, Human immunodeficiency virus 2; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D003545:Cysteine