Flexible docking of pyridinone derivatives into the non-nucleoside inhibitor binding site of HIV-1 reverse transcriptase

2004 ◽  
Vol 12 (23) ◽  
pp. 6085-6095 ◽  
Author(s):  
José Luis Medina-Franco ◽  
Sergio Rodrı́guez-Morales ◽  
Cecilia Juárez-Gordiano ◽  
Alicia Hernández-Campos ◽  
Jesús Jiménez-Barbero ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Binding Site ◽  
Flexible Docking ◽  
Inhibitor Binding ◽  
Hiv 1

All-Atom Models for the Non-Nucleoside Binding Site of HIV-1 Reverse Transcriptase Complexed with Inhibitors:  A 3D QSAR Approach†

1996 ◽  
Vol 39 (8) ◽  
pp. 1645-1650 ◽  
Author(s):  
Rick Gussio ◽  
Nagarajan Pattabiraman ◽  
Daniel W. Zaharevitz ◽  
Glen E. Kellogg ◽  
Igor A. Topol ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Binding Site ◽  
3D Qsar ◽  
Hiv 1

scholarly journals Efavirenz Binding Site in HIV-1 Reverse Transcriptase Monomers

Biochemistry ◽  
2010 ◽  
Vol 49 (49) ◽  
pp. 10565-10573 ◽  
Author(s):  
Valerie A. Braz ◽  
Mary D. Barkley ◽  
Rebecca A. Jockusch ◽  
Patrick L. Wintrode
Keyword(s):  
Reverse Transcriptase ◽  
Binding Site ◽  
Hiv 1

scholarly journals Theoretical studies of energetics and binding isotope effects of binding a triazole-based inhibitor to HIV-1 reverse transcriptase

2016 ◽  
Vol 18 (1) ◽  
pp. 310-317 ◽  
Author(s):  
A. Krzemińska ◽  
K. P. Świderek ◽  
P. Paneth
Keyword(s):  
Reverse Transcriptase ◽  
Binding Site ◽  
Isotope Effect ◽  
Isotope Effects ◽  
Theoretical Studies ◽  
Hiv 1

The 18O binding isotope effect allows us to distinguish the actual binding site of an inhibitor in HIV-1 reverse transcriptase.

scholarly journals The Phenylmethylthiazolylthiourea Nonnucleoside Reverse Transcriptase (RT) Inhibitor MSK-076 Selects for a Resistance Mutation in the Active Site of Human Immunodeficiency Virus Type 2 RT

2004 ◽  
Vol 78 (14) ◽  
pp. 7427-7437 ◽  
Author(s):  
Joeri Auwerx ◽  
Miguel Stevens ◽  
An R. Van Rompay ◽  
Louise E. Bird ◽  
Jingshan Ren ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Binding Site ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Active Site ◽  
Resistance Mutation ◽  
Site Directed Mutagenesis ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The phenylmethylthiazolylthiourea (PETT) derivative MSK-076 shows, besides high potency against human immunodeficiency virus type 1 (HIV-1), marked activity against HIV-2 (50% effective concentration, 0.63 μM) in cell culture. Time-of-addition experiments pointed to HIV-2 reverse transcriptase (RT) as the target of action of MSK-076. Recombinant HIV-2 RT was inhibited by MSK-076 at 23 μM. As was also found for HIV-1 RT, MSK-076 inhibited HIV-2 RT in a noncompetitive manner with respect to dGTP and poly(rC)·oligo(dG) as the substrate and template-primer, respectively. MSK-076 selected for A101P and G112E mutations in HIV-2 RT and for K101E, Y181C, and G190R mutations in HIV-1 RT. The selected mutated strains of HIV-2 were fully resistant to MSK-076, and the mutant HIV-2 RT enzymes into which the A101P and/or G112E mutation was introduced by site-directed mutagenesis showed more than 50-fold resistance to MSK-076. Mapping of the resistance mutations to the HIV-2 RT structure ascertained that A101P is located at a position equivalent to the nonnucleoside RT inhibitor (NNRTI)-binding site of HIV-1 RT. G112E, however, is distal to the putative NNRTI-binding site in HIV-2 RT but close to the active site, implying a novel molecular mode of action and mechanism of resistance. Our findings have important implications for the development of new NNRTIs with pronounced activity against a wider range of lentiviruses.

A novel inhibitor-binding site on the HIV-1 capsid N-terminal domain leads to improved crystallizationviacompound-mediated dimerization

2013 ◽  
Vol 69 (6) ◽  
pp. 1115-1123 ◽  
Author(s):  
Christopher T. Lemke ◽  
Steve Titolo ◽  
Nathalie Goudreau ◽  
Anne-Marie Faucher ◽  
Stephen W. Mason ◽  
...  
Keyword(s):  
Binding Site ◽  
Inhibitor Binding ◽  
Terminal Domain ◽  
Hiv 1

scholarly journals Mutations in the U5 Region Adjacent to the Primer Binding Site Affect tRNA Cleavage by Human Immunodeficiency Virus Type 1 Reverse Transcriptase In Vivo

2007 ◽  
Vol 82 (2) ◽  
pp. 719-727 ◽  
Author(s):  
Jangsuk Oh ◽  
Mary Jane McWilliams ◽  
John G. Julias ◽  
Stephen H. Hughes
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Binding Site ◽  
Rnase H ◽  
Primer Binding Site ◽  
Cleavage Specificity ◽  
Immunodeficiency Virus ◽  
Trna Primer ◽  
Hiv 1

ABSTRACT In retroviruses, the first nucleotide added to the tRNA primer defines the end of the U5 region in the right long terminal repeat, and the subsequent removal of this tRNA primer by RNase H exactly defines the U5 end of the linear double-stranded DNA. In most retroviruses, the entire tRNA is removed by RNase H cleavage at the RNA/DNA junction. However, the RNase H domain of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase cleaves the tRNA 1 nucleotide from the RNA/DNA junction at the U5/primer binding site (PBS) junction, which leaves an rA residue at the U5 terminus. We made sequence changes at the end of the U5 region adjacent to the PBS in HIV-1 to determine whether such changes affect the specificity of tRNA primer cleavage by RNase H. In some of the mutants, RNase H usually removed the entire tRNA, showing that the cleavage specificity was shifted by 1 nucleotide. This result suggests that the tRNA cleavage specificity of the HIV-1 RNase domain H depends on sequences in U5.

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