ArticleJournal of virology2002
Altered substrate specificity of drug-resistant human immunodeficiency virus type 1 protease.
Article in Journal of virology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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.
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Who cites it
24 citing papers in PubMed, 56 citations in OpenAlex.
- A human endogenous retrovirus encoded protease potentially cleaves numerous cellular proteins.Mobile DNA · 2019Article
- Fluorometric assay for phenotypic differentiation of drug-resistant HIV mutants.Scientific reports · 2015Article
- Resistance mechanism of human immunodeficiency virus type-1 protease to inhibitors: A molecular dynamic approach.Molecular biology research communications · 2014Article
- Differential impact of resistance-associated mutations to protease inhibitors and nonnucleoside reverse transcriptase inhibitors on HIV-1 replication capacity.AIDS research and human retroviruses · 2013Article
- Mutations in multiple domains of Gag drive the emergence of in vitro resistance to the phosphonate-containing HIV-1 protease inhibitor GS-8374.Journal of virology · 2013Article
- Context surrounding processing sites is crucial in determining cleavage rate of a subset of processing sites in HIV-1 Gag and Gag-Pro-Pol polyprotein precursors by viral protease.The Journal of biological chemistry · 2012Article
- Prediction of mutational tolerance in HIV-1 protease and reverse transcriptase using flexible backbone protein design.PLoS computational biology · 2012Article
- Predicting human immunodeficiency virus protease cleavage sites in nonlinear projection space.Molecular and cellular biochemistry · 2010Article
- Identification of structural mechanisms of HIV-1 protease specificity using computational peptide docking: implications for drug resistance.Structure (London, England : 1993) · 2009Article
- A look inside HIV resistance through retroviral protease interaction maps.PLoS computational biology · 2007Article
- A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism.PLoS medicine · 2007Article
- Comprehensive bioinformatic analysis of the specificity of human immunodeficiency virus type 1 protease.Journal of virology · 2005Article
- Atazanavir signature I50L resistance substitution accounts for unique phenotype of increased susceptibility to other protease inhibitors in a variety of human immunodeficiency virus type 1 genetic backbones.Antimicrobial agents and chemotherapy · 2005Article
- Evolution of human immunodeficiency virus type 1 protease genotypes and phenotypes in vivo under selective pressure of the protease inhibitor ritonavir.Journal of virology · 2005Article
- Structural basis for coevolution of a human immunodeficiency virus type 1 nucleocapsid-p1 cleavage site with a V82A drug-resistant mutation in viral protease.Journal of virology · 2004Article
- Role of minority populations of human immunodeficiency virus type 1 in the evolution of viral resistance to protease inhibitors.Journal of virology · 2004Article
- The Clinical Implications of Reduced Viral Fitness.Current infectious disease reports · 2004Article
- Crystal structures of a multidrug-resistant human immunodeficiency virus type 1 protease reveal an expanded active-site cavity.Journal of virology · 2004Article
- Gag non-cleavage site mutations contribute to full recovery of viral fitness in protease inhibitor-resistant human immunodeficiency virus type 1.Antimicrobial agents and chemotherapy · 2004Article
- Infectivity and replication capacity of drug-resistant human immunodeficiency virus type 1 variants isolated during primary infection.Journal of virology · 2003Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Resistance to human immunodeficiency virus type 1 protease (HIV PR) inhibitors results primarily from the selection of multiple mutations in the protease region. Because many of these mutations are selected for the ability to decrease inhibitor binding in the active site, they also affect substrate binding and potentially substrate specificity. This work investigates the substrate specificity of a panel of clinically derived protease inhibitor-resistant HIV PR variants. To compare protease specificity, we have used positional-scanning, synthetic combinatorial peptide libraries as well as a select number of individual substrates. The subsite preferences of wild-type HIV PR determined by using the substrate libraries are consistent with prior reports, validating the use of these libraries to compare specificity among a panel of HIV PR variants. Five out of seven protease variants demonstrated subtle differences in specificity that may have significant impacts on their abilities to function in viral maturation. Of these, four variants demonstrated up to fourfold changes in the preference for valine relative to alanine at position P2 when tested on individual peptide substrates. This change correlated with a common mutation in the viral NC/p1 cleavage site. These mutations may represent a mechanism by which severely compromised, drug-resistant viral strains can increase fitness levels. Understanding the altered substrate specificity of drug-resistant HIV PR should be valuable in the design of future generations of protease inhibitors as well as in elucidating the molecular basis of regulation of proteolysis in HIV.
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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.