ArticleActa crystallographica. Section D, Biological crystallography2011
Contribution of the 80s loop of HIV-1 protease to the multidrug-resistance mechanism: crystallographic study of MDR769 HIV-1 protease variants.
Article in Acta crystallographica. Section D, Biological crystallography, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Advancements in development of novel class of HIV protease inhibitors.Annals of medicine · 2026Review
- HIV-1 protease with 10 lopinavir and darunavir resistance mutations exhibits altered inhibition, structural rearrangements and extreme dynamics.Journal of molecular graphics & modelling · 2022Article
- Structural Impacts of Drug-Resistance Mutations Appearing in HIV-2 Protease.Molecules (Basel, Switzerland) · 2021Article
- Potent antiviral HIV-1 protease inhibitor combats highly drug resistant mutant PR20.Biochemical and biophysical research communications · 2019Article
- Highly Drug-Resistant HIV-1 Protease Mutant PRS17 Shows Enhanced Binding to Substrate Analogues.ACS omega · 2019Article
- GRL-09510, a Unique P2-Crown-Tetrahydrofuranylurethane -Containing HIV-1 Protease Inhibitor, Maintains Its Favorable Antiviral Activity against Highly-Drug-Resistant HIV-1 Variants in vitro.Scientific reports · 2017Article
- The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops.Biochemistry and biophysics reports · 2015Article
- Highly resistant HIV-1 proteases and strategies for their inhibition.Future medicinal chemistry · 2015Review
- The role of mutations at codons 32, 47, 54, and 90 in HIV-1 protease flap dynamics.Discoveries (Craiova, Romania) · 2014Article
- A multi-drug resistant HIV-1 protease is resistant to the dimerization inhibitory activity of TLF-PafF.Journal of molecular graphics & modelling · 2014Article
- Building on Cram's legacy: stimulated gating in hemicarcerands.Accounts of chemical research · 2014Article
- A conserved hydrogen-bonding network of P2 bis-tetrahydrofuran-containing HIV-1 protease inhibitors (PIs) with a protease active-site amino acid backbone aids in their activity against PI-resistant HIV.Antimicrobial agents and chemotherapy · 2014Article
- P1 and P1' para-fluoro phenyl groups show enhanced binding and favorable predicted pharmacological properties: structure-based virtual screening of extended lopinavir analogs against multi-drug resistant HIV-1 protease.Journal of molecular graphics & modelling · 2014Article
- P2' benzene carboxylic acid moiety is associated with decrease in cellular uptake: evaluation of novel nonpeptidic HIV-1 protease inhibitors containing P2 bis-tetrahydrofuran moiety.Antimicrobial agents and chemotherapy · 2013Article
- Design, synthesis and evaluation of a potent substrate analog inhibitor identified by scanning Ala/Phe mutagenesis, mimicking substrate co-evolution, against multidrug-resistant HIV-1 protease.Biochemical and biophysical research communications · 2013Article
- Crystallographic study of multi-drug resistant HIV-1 protease lopinavir complex: mechanism of drug recognition and resistance.Biochemical and biophysical research communications · 2013Article
- Conserved hydrogen bonds and water molecules in MDR HIV-1 protease substrate complexes.Biochemical and biophysical research communications · 2013Article
- Crystal structures of multidrug-resistant HIV-1 protease in complex with two potent anti-malarial compounds.Biochemical and biophysical research communications · 2012Article
- The higher barrier of darunavir and tipranavir resistance for HIV-1 protease.Biochemical and biophysical research communications · 2011Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The flexible flaps and the 80s loops (Pro79-Ile84) of HIV-1 protease are crucial in inhibitor binding. Previously, it was reported that the crystal structure of multidrug-resistant 769 (MDR769) HIV-1 protease shows a wide-open conformation of the flaps owing to conformational rigidity acquired by the accumulation of mutations. In the current study, the effect of mutations on the conformation of the 80s loop of MDR769 HIV-1 protease variants is reported. Alternate conformations of Pro81 (proline switch) with a root-mean-square deviation of 3-4.8 Å in the C(α) atoms of the I10V mutant and a side chain with a `flipped-out' conformation in the A82F mutant cause distortion in the S1/S1' binding pockets that affects inhibitor binding. The A82S and A82T mutants show local changes in the electrostatics of inhibitor binding owing to the mutation from nonpolar to polar residues. In summary, the crystallographic studies of four variants of MDR769 HIV-1 protease presented in this article provide new insights towards understanding the drug-resistance mechanism as well as a basis for design of future protease inhibitors with enhanced potency.
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