ArticleProtein science : a publication of the Protein Society1999
Drug resistance mutations can effect dimer stability of HIV-1 protease at neutral pH.
Article in Protein science : a publication of the Protein Society, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed.
- Inhibitor-induced dimerization mediates lufotrelvir resistance in mutants of SARS-CoV-2 3C-like protease.Protein science : a publication of the Protein Society · 2025Article
- Structural Impacts of Drug-Resistance Mutations Appearing in HIV-2 Protease.Molecules (Basel, Switzerland) · 2021Article
- Article
- Resistance mechanism of human immunodeficiency virus type-1 protease to inhibitors: A molecular dynamic approach.Molecular biology research communications · 2014Article
- Substrate envelope-designed potent HIV-1 protease inhibitors to avoid drug resistance.Chemistry & biology · 2013Article
- Thermodynamics of strongly allosteric inhibition: a model study of HIV-1 protease.European biophysics journal : EBJ · 2012Article
- Protein intrinsic disorder as a flexible armor and a weapon of HIV-1.Cellular and molecular life sciences : CMLS · 2012Review
- Accessory mutations maintain stability in drug-resistant HIV-1 protease.Journal of molecular biology · 2011Article
- Article
- Patterns of Human Immunodeficiency Virus type 1 recombination ex vivo provide evidence for coadaptation of distant sites, resulting in purifying selection for intersubtype recombinants during replication.Journal of virology · 2010Article
- The folding free-energy surface of HIV-1 protease: insights into the thermodynamic basis for resistance to inhibitors.Journal of molecular biology · 2009Article
- Effect of the active site D25N mutation on the structure, stability, and ligand binding of the mature HIV-1 protease.The Journal of biological chemistry · 2008Article
- Insight into the folding inhibition of the HIV-1 protease by a small peptide.Biophysical journal · 2007Article
- Role of invariant Thr80 in human immunodeficiency virus type 1 protease structure, function, and viral infectivity.Journal of virology · 2006Article
- Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S.Journal of molecular biology · 2005Article
- Design of HIV-1-PR inhibitors that do not create resistance: blocking the folding of single monomers.Protein science : a publication of the Protein Society · 2005Article
- Complementation in cells cotransfected with a mixture of wild-type and mutant human immunodeficiency virus (HIV) influences the replication capacities and phenotypes of mutant variants in a single-cycle HIV resistance assay.Journal of clinical microbiology · 2004Article
- Kinetics of the dimerization of retroviral proteases: the "fireman's grip" and dimerization.Protein science : a publication of the Protein Society · 2003Article
- Human immunodeficiency virus (HIV) type 1 transframe protein can restore activity to a dimerization-deficient HIV protease variant.Journal of virology · 2003Article
- Structure-based phenotyping predicts HIV-1 protease inhibitor resistance.Protein science : a publication of the Protein Society · 2003Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
The monomer-dimer equilibrium for the human immunodeficiency virus type 1 (HIV-1) protease has been investigated under physiological conditions. Dimer dissociation at pH 7.0 was correlated with a loss in beta-sheet structure and a lower degree of ANS binding. An autolysis-resistant mutant, Q7K/L33I/L63I, was used to facilitate sedimentation equilibrium studies at neutral pH where the wild-type enzyme is typically unstable in the absence of bound inhibitor. The dimer dissociation constant (KD) of the triple mutant was 5.8 microM at pH 7.0 and was below the limit of measurement (approximately 100 nM) at pH 4.5. Similar studies using the catalytically inactive D25N mutant yielded a KD value of 1.0 microM at pH 7.0. These values differ significantly from a previously reported value of 23 nM obtained indirectly from inhibitor binding measurements (Darke et al., 1994). We show that the discrepancy may result from the thermodynamic linkage between the monomer-dimer and inhibitor binding equilibria. Under conditions where a significant degree of monomer is present, both substrates and competitive inhibitors will shift the equilibrium toward the dimer, resulting in apparent increases in dimer stability and decreases in ligand binding affinity. Sedimentation equilibrium studies were also carried out on several drug-resistant HIV-1 protease mutants: V82F, V82F/I84V, V82T/I84V, and L90M. All four mutants exhibited reduced dimer stability relative to the autolysis-resistant mutant at pH 7.0. Our results indicate that reductions in drug affinity may be due to the combined effects of mutations on both dimer stability and inhibitor binding.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.