Intramolecular Chimeras of the p51 Subunit between HIV-1 and FIV Reverse Transcriptases Suggest a Stabilizing Function for the p66 Subunit in the Heterodimeric Enzyme†

Biochemistry ◽  
1999 ◽  
Vol 38 (5) ◽  
pp. 1633-1642 ◽  
Author(s):  
Taurai Tasara ◽  
Mario Amacker ◽  
Ulrich Hübscher
Keyword(s):  
Reverse Transcriptases ◽  
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

Quantitative analysis of the interactions between HIV-1 integrase and retroviral reverse transcriptases

2008 ◽  
Vol 412 (1) ◽  
pp. 163-170 ◽  
Author(s):  
Alon Herschhorn ◽  
Iris Oz-Gleenberg ◽  
Amnon Hizi
Keyword(s):  
Conformational Changes ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Reaction Model ◽  
Protein Protein Interactions ◽  
Common Site ◽  
Leukaemia Virus ◽  
Reverse Transcriptases ◽  
Interaction Kinetics ◽  
Hiv 1

The RT (reverse transcriptase) of HIV-1 interacts with HIV-1 IN (integrase) and inhibits its enzymatic activities. However, the molecular mechanisms underling these interactions are not well understood. In order to study these mechanisms, we have analysed the interactions of HIV-1 IN with HIV-1 RT and with two other related RTs: those of HIV-2 and MLV (murine-leukaemia virus). All three RTs inhibited HIV-1 IN, albeit to a different extent, suggesting a common site of binding that could be slightly modified for each one of the studied RTs. Using surface plasmon resonance technology, which monitors direct protein–protein interactions, we performed kinetic analyses of the binding of HIV-1 IN to these three RTs and observed interesting binding patterns. The interaction of HIV-1 RT with HIV-1 IN was unique and followed a two-state reaction model. According to this model, the initial IN–RT complex formation was followed by a conformational change in the complex that led to an elevation of the total affinity between these two proteins. In contrast, HIV-2 and MLV RTs interacted with IN in a simple bi-molecular manner, without any apparent secondary conformational changes. Interestingly, HIV-1 and HIV-2 RTs were the most efficient inhibitors of HIV-1 IN activity, whereas HIV-1 and MLV RTs showed the highest affinity towards HIV-1 IN. These modes of direct protein interactions, along with the apparent rate constants calculated and the correlations of the interaction kinetics with the capacity of the RTs to inhibit IN activities, are all discussed.

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 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.

HIV-1 and HIV-2 reverse transcriptases: A comparative study of sensitivity to inhibition by selected natural products

1992 ◽  
Vol 185 (1) ◽  
pp. 370-378 ◽  
Author(s):  
Ghee T. Tan ◽  
James F. Miller ◽  
A. Douglas Kinghorn ◽  
Stephen H. Hughes ◽  
John M. Pezzuto
Keyword(s):  
Natural Products ◽  
Comparative Study ◽  
Reverse Transcriptases ◽  
Hiv 1

scholarly journals Molecular Determinants of Multi-nucleoside Analogue Resistance in HIV-1 Reverse Transcriptases Containing a Dipeptide Insertion in the Fingers Subdomain

2004 ◽  
Vol 279 (23) ◽  
pp. 24569-24577 ◽  
Author(s):  
Tania Matamoros ◽  
Sandra Franco ◽  
Blanca M. Vázquez-Álvarez ◽  
Antonio Mas ◽  
Miguel Ángel Martínez ◽  
...  
Keyword(s):  
Nucleoside Analogue ◽  
Reverse Transcriptases ◽  
Molecular Determinants ◽  
Hiv 1
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