scholarly journals The effects of cysteine mutations on the reverse transcriptases of human immunodeficiency virus types 1 and 2.

1992 ◽  
Vol 267 (2) ◽  
pp. 1293-1297
Author(s):  
A Hizi ◽  
M Shaharabany ◽  
R Tal ◽  
S H Hughes
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptases ◽  
Immunodeficiency Virus

scholarly journals Crystal Structures of Zidovudine- or Lamivudine-Resistant Human Immunodeficiency Virus Type 1 Reverse Transcriptases Containing Mutations at Codons 41, 184, and 215

2002 ◽  
Vol 76 (19) ◽  
pp. 10015-10019 ◽  
Author(s):  
P. P. Chamberlain ◽  
J. Ren ◽  
C. E. Nichols ◽  
L. Douglas ◽  
J. Lennerstrand ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Conformational Changes ◽  
Model Building ◽  
Resistance Mutations ◽  
Reverse Transcriptases ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Six structures of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) containing combinations of resistance mutations for zidovudine (AZT) (M41L and T215Y) or lamivudine (M184V) have been determined as inhibitor complexes. Minimal conformational changes in the polymerase or nonnucleoside RT inhibitor sites compared to the mutant RTMC (D67N, K70R, T215F, and K219N) are observed, indicating that such changes may occur only with certain combinations of mutations. Model building M41L and T215Y into HIV-1 RT-DNA and docking in ATP that is utilized in the pyrophosphorolysis reaction for AZT resistance indicates that some conformational rearrangement appears necessary in RT for ATP to interact simultaneously with the M41L and T215Y mutations.

scholarly journals Increased G→A Transition Frequencies Displayed by Primer Grip Mutants of Human Immunodeficiency Virus Type 1 Reverse Transcriptase

2004 ◽  
Vol 78 (2) ◽  
pp. 1012-1019 ◽  
Author(s):  
Clara E. Cases-González ◽  
Luis Menéndez-Arias
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Target Sequence ◽  
Strand Transfer ◽  
Wild Type ◽  
Reverse Transcriptases ◽  
Immunodeficiency Virus ◽  
Reported Data

ABSTRACT A genetic screen based on the blue-white β-galactosidase complementation assay designed to detect G→A mutations arising during RNA-dependent DNA synthesis was used to compare the fidelity of mutant human immunodeficiency virus type 1 reverse transcriptases (RTs) with the mutations M230L and M230I with the wild-type enzyme, in the presence of biased deoxynucleoside triphosphate (dNTP) pools. The mutant RTs with the M230L and M230I changes were found to be 20 to 70 times less faithful than the wild-type RT in the presence of low [dCTP]/[dTTP] ratios but showed similar fidelity in assays carried out with equimolar concentrations of each nucleotide. Biased dNTP pools led to short tandem repeat deletions in the target sequence, which were also detectable with the assay. However, deletion frequencies were similar for all of the RTs tested. The reported data suggest that RT pausing due to the low dNTP levels available in the RT reaction mixture facilitates strand transfer, in a process that is not necessarily mediated by nucleotide misinsertion.

scholarly journals Characterization of HIV Reverse Transcriptases with Tyr181→Cys and Leu100→lle Mutations

1993 ◽  
Vol 4 (5) ◽  
pp. 301-308 ◽  
Author(s):  
H. Zhang ◽  
L. Vrang ◽  
T. Unge ◽  
B. Öberg
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mixed Type ◽  
Competitive Inhibition ◽  
Wild Type ◽  
Hiv Reverse Transcriptase ◽  
Reverse Transcriptases ◽  
Immunodeficiency Virus ◽  
Hiv Rt ◽  
Rt Inhibitors

Two mutants of human immunodeficiency virus (HIV) reverse transcriptase (RT), Tyr181 to Cys and Leu100 to He, have been prepared and characterized by use of various inhibitors. As compared to wild type RT the mutant RT's had lower Kcat/Km values. The Km values were lower with heteropolymeric than with homopolymeric template-primers. Inhibition by phosphonoformate was of mixed type with both wild-type and mutant RT's and the mutants were less sensitive to phosphonoformate than the wild type RT. The non-nucleoside RT inhibitors 9-CI-TIBO and L-697,661 gave a non-competitive inhibition with respect to substrate of the wild type RT. The mutant RT's were inhibited at higher concentrations, showing a mixed type of inhibition with respect to substrate. ddGTP caused a competitive inhibition of wild type and mutant RT's with respect to substrate. RT preparations with different mutations are useful in rapidly characterizing the interaction between various inhibitors and HIV RT and thus facilitate the development of new inhibitors.

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