ArticleThe Journal of biological chemistry2006
Identification of amino acids in HIV-1 and avian sarcoma virus integrase subsites required for specific recognition of the long terminal repeat Ends.
Article in The Journal of biological chemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 63 citations in OpenAlex.
- Application of Amino Acids in the Structural Modification of Natural Products: A Review.Frontiers in chemistry · 2021Review
- NKNK: a New Essential Motif in the C-Terminal Domain of HIV-1 Group M Integrases.Journal of virology · 2020Article
- Raltegravir-Induced Adaptations of the HIV-1 Integrase: Analysis of Structure, Variability, and Mutation Co-occurrence.Frontiers in microbiology · 2019Article
- Degradation and remobilization of endogenous retroviruses by recombination during the earliest stages of a germ-line invasion.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Current Peptide and Protein Candidates Challenging HIV Therapy beyond the Vaccine Era.Viruses · 2017Review
- Cryo-EM structures and atomic model of the HIV-1 strand transfer complex intasome.Science (New York, N.Y.) · 2017Article
- Crosslinking and mass spectrometry suggest that the isolated NTD domain dimer of Moloney murine leukemia virus integrase adopts a parallel arrangement in solution.BMC structural biology · 2013Article
- A homology model of HIV-1 integrase and analysis of mutations designed to test the model.Journal of molecular biology · 2013Article
- Dolutegravir interactions with HIV-1 integrase-DNA: structural rationale for drug resistance and dissociation kinetics.PloS one · 2013Article
- Retroviral integrases promote fraying of viral DNA ends.The Journal of biological chemistry · 2011Article
- Structural biology of retroviral DNA integration.Virology · 2011Review
- Localization of ASV integrase-DNA contacts by site-directed crosslinking and their structural analysis.PloS one · 2011Article
- Structure-based modeling of the functional HIV-1 intasome and its inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Computer tools in the discovery of HIV-1 integrase inhibitors.Future medicinal chemistry · 2010Review
- Resistance to integrase inhibitors.Viruses · 2010Article
- Structural properties of HIV integrase. Lens epithelium-derived growth factor oligomers.The Journal of biological chemistry · 2010Article
- Impact of Y143 HIV-1 integrase mutations on resistance to raltegravir in vitro and in vivo.Antimicrobial agents and chemotherapy · 2010Article
- Inhibition of HIV-1 integrase nuclear import and replication by a peptide bearing integrase putative nuclear localization signal.Retrovirology · 2009Article
- HIV-1 Integrase-DNA Recognition Mechanisms.Viruses · 2009Article
- Specificity of LTR DNA recognition by a peptide mimicking the HIV-1 integrase {alpha}4 helix.Nucleic acids research · 2009Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
A tetramer model for HIV-1 integrase (IN) with DNA representing 20 bp of the U3 and U5 long terminal repeats (LTR) termini was assembled using structural and biochemical data and molecular dynamics simulations. It predicted amino acid residues on the enzyme surface that can interact with the LTR termini. A separate structural alignment of HIV-1, simian sarcoma virus (SIV), and avian sarcoma virus (ASV) INs predicted which of these residues were unique. To determine whether these residues were responsible for specific recognition of the LTR termini, the amino acids from ASV IN were substituted into the structurally equivalent positions of HIV-1 IN, and the ability of the chimeras to 3 ' process U5 HIV-1 or ASV duplex oligos was determined. This analysis demonstrated that there are multiple amino acid contacts with the LTRs and that substitution of ASV IN amino acids at many of the analogous positions in HIV-1 IN conferred partial ability to cleave ASV substrates with a concomitant loss in the ability to cleave the homologous HIV-1 substrate. HIV-1 IN residues that changed specificity include Val(72), Ser(153), Lys(160)-Ile(161), Gly(163)-Val(165), and His(171)-Leu(172). Because a chimera that combines several of these substitutions showed a specificity of cleavage of the U5 ASV substrate closer to wild type ASV IN compared with chimeras with individual amino acid substitutions, it appears that the sum of the IN interactions with the LTRs determines the specificity. Finally, residues Ser(153) and Val(72) in HIV-1 IN are among those that change in enzymes that develop resistance to naphthyridine carboxamide- and diketo acid-related inhibitors in cells. Thus, amino acid residues involved in recognition of the LTRs are among these positions that change in development of drug resistance.
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