Fidelity of Mutant HIV-1 Reverse Transcriptases:  Interaction with the Single-Stranded Template Influences the Accuracy of DNA Synthesis†

Biochemistry ◽  
1998 ◽  
Vol 37 (17) ◽  
pp. 5831-5839 ◽  
Author(s):  
Baek Kim ◽  
Tanya R. Hathaway ◽  
Lawrence A. Loeb
Keyword(s):  
Dna Synthesis ◽  
Reverse Transcriptases ◽  
Hiv 1

scholarly journals Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis

2013 ◽  
Vol 41 (8) ◽  
pp. 4601-4612 ◽  
Author(s):  
Mar Álvarez ◽  
Verónica Barrioluengo ◽  
Raquel N. Afonso-Lehmann ◽  
Luis Menéndez-Arias
Keyword(s):  
Dna Synthesis ◽  
Rnase H ◽  
Reverse Transcriptases ◽  
Hiv 1

scholarly journals Structures of Complexes Formed by HIV-1 Reverse Transcriptase at a Termination Site of DNA Synthesis

2001 ◽  
Vol 276 (33) ◽  
pp. 31439-31448 ◽  
Author(s):  
Marc Lavigne ◽  
Lucette Polomack ◽  
Henri Buc
Keyword(s):  
Reverse Transcriptase ◽  
Dna Synthesis ◽  
Hiv 1

scholarly journals Mutating a Region of HIV-1 Reverse Transcriptase Implicated in tRNALys-3Binding and the Consequences for (−)-Strand DNA Synthesis

1998 ◽  
Vol 273 (23) ◽  
pp. 14523-14532 ◽  
Author(s):  
Eric J. Arts ◽  
Jennifer T. Miller ◽  
Bernard Ehresmann ◽  
Stuart F. J. Le Grice
Keyword(s):  
Reverse Transcriptase ◽  
Dna Synthesis ◽  
Hiv 1

Thiotetrazole alkynylacetanilides as potent and bioavailable non-nucleoside inhibitors of the HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases

2007 ◽  
Vol 17 (16) ◽  
pp. 4437-4441 ◽  
Author(s):  
Alexandre Gagnon ◽  
Ma’an H. Amad ◽  
Pierre R. Bonneau ◽  
René Coulombe ◽  
Patrick L. DeRoy ◽  
...  
Keyword(s):  
Double Mutant ◽  
Wild Type ◽  
Reverse Transcriptases ◽  
Nucleoside Inhibitors ◽  
Hiv 1

The double mutation L109M and R448M of HIV-1 reverse transcriptase decreases fidelity of DNA synthesis by promoting mismatch elongation

2015 ◽  
Vol 396 (12) ◽  
pp. 1315-1323
Author(s):  
Bianca Heyn ◽  
Nicole Pogodalla ◽  
Susanne Brakmann
Keyword(s):  
Reverse Transcriptase ◽  
Dna Synthesis ◽  
Error Rate ◽  
Double Mutant ◽  
Dissociation Rate ◽  
Double Mutation ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Simultaneous Substitution

Abstract Changes of Leu109 and Arg448 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) have as yet not been associated with altered fitness. However, in a recent study, we described that the simultaneous substitution of L109 and R448 by methionine leads to an error-producing polymerase phenotype that is not observed for the isolated substitutions. The double mutant increased the error rate of DNA-dependent DNA synthesis 3.1-fold as compared to the wildtype enzyme and showed a mutational spectrum with a fraction of 28% frameshift mutations and 48% transitions. We show here that weaker binding of DNA:DNA primer-templates as indicated by an increased dissociation rate constant (koff) could account for the higher frameshift error rate. Furthermore, we were able to explain the prevalence of transition mutations with the finding that HIV-1 RT variant L109M/R448M preferred misincorporation of C opposite A and elongation of C:A mismatches.

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