Mutated K65R recombinant reverse transcriptase of human immunodeficiency virus type 1 shows diminished chain termination in the presence of 2',3'-dideoxycytidine 5'-triphosphate and other drugs.

Abstract:

:A lysine-to-arginine substitution at amino acid 65 (K65R) in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is associated with resistance to 2',3'-dideoxycytidine (ddC), 2',3'-dideoxyinosine (ddI), and the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine (3TC). To further characterize the molecular basis of such resistance, we expressed the pp6/p51 heterodimer of wild-type RT, K65R mutated RT, and a doubly mutated (K65R/M184V) RT in Escherichia coli and assessed the characteristics of nucleotide incorporation and chain termination in cell-free reverse transcription reactions in the presence and absence of various nucleoside triphosphate analogs. These reactions employed a HIV RNA template (HIV-PBS) that contained the primer binding sequence (PBS) and the U5 and R regions of HIV-1 genomic RNA and an oligodeoxynucleotide (dPR) complementary to the HIV-1 PBS as primer. The K65R and K65R/M184V RTs showed significantly decreased chain-termination effects during polymerization with the 5'-triphosphates of ddC, 3TC, 2',3'-dideoxyadenosine, and AZT (3'-azido-3'-deoxythymidine) in comparison with wild-type RT. Detailed analysis with ddCTP and wild-type RT revealed that chain termination occurred at all guanines in the RNA template. However, the frequency of dideoxynucleoside triphosphate (ddNTP)-induced chain termination was decreased at certain guanines but not others in reactions catalyzed by K65R RT. Both the K65R mutant RT and wild-type RT had similar processive activity. These results indicate that decreased chain termination of K65R RT in the presence of ddNTPs is consistent with data obtained in viral replication assays.

authors

Gu Z,Arts EJ,Parniak MA,Wainberg MA

doi

10.1073/pnas.92.7.2760

subject

Has Abstract

pub_date

1995-03-28 00:00:00

pages

2760-4

issue

7

eissn

0027-8424

issn

1091-6490

journal_volume

92

pub_type

杂志文章
  • Adaptive evolution of cytochrome c oxidase: Infrastructure for a carnivorous plant radiation.

    abstract::Much recent attention in the study of adaptation of organismal form has centered on developmental regulation. As such, the highly conserved respiratory machinery of eukaryotic cells might seem an unlikely target for selection supporting novel morphologies. We demonstrate that a dramatic molecular evolutionary rate inc...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0408092101

    authors: Jobson RW,Nielsen R,Laakkonen L,Wikström M,Albert VA

    更新日期:2004-12-28 00:00:00

  • Mating-type switching by chromosomal inversion in methylotrophic yeasts suggests an origin for the three-locus Saccharomyces cerevisiae system.

    abstract::Saccharomyces cerevisiae has a complex system for switching the mating type of haploid cells, requiring the genome to have three mating-type (MAT)-like loci and a mechanism for silencing two of them. How this system originated is unknown, because the three-locus system is present throughout the family Saccharomycetace...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1416014111

    authors: Hanson SJ,Byrne KP,Wolfe KH

    更新日期:2014-11-11 00:00:00

  • Resident macrophages of pancreatic islets have a seminal role in the initiation of autoimmune diabetes of NOD mice.

    abstract::Treatment of C57BL/6 or NOD mice with a monoclonal antibody to the CSF-1 receptor resulted in depletion of the resident macrophages of pancreatic islets of Langerhans that lasted for several weeks. Depletion of macrophages in C57BL/6 mice did not affect multiple parameters of islet function, including glucose response...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1713543114

    authors: Carrero JA,McCarthy DP,Ferris ST,Wan X,Hu H,Zinselmeyer BH,Vomund AN,Unanue ER

    更新日期:2017-11-28 00:00:00

  • SLC4A2-mediated Cl-/HCO3- exchange activity is essential for calpain-dependent regulation of the actin cytoskeleton in osteoclasts.

    abstract::Bone remodeling requires osteoclasts to generate and maintain an acidified resorption compartment between the apical membrane and the bone surface to solubilize hydroxyapatite crystals within the bone matrix. This acidification process requires (i) apical proton secretion by a vacuolar H(+)-ATPase, (ii) actin cytoskel...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1206392110

    authors: Coury F,Zenger S,Stewart AK,Stephens S,Neff L,Tsang K,Shull GE,Alper SL,Baron R,Aliprantis AO

    更新日期:2013-02-05 00:00:00

  • Heterozygous alpha 2A-adrenergic receptor mice unveil unique therapeutic benefits of partial agonists.

    abstract::Genetic manipulation of the alpha(2A)-adrenergic receptor (alpha(2A)-AR) in mice has revealed the role of this subtype in numerous responses, including agonist-induced hypotension and sedation. Unexpectedly, alpha(2)-agonist treatment of mice heterozygous for the alpha(2A)-AR (alpha(2A)-AR(+/-)) lowers blood pressure ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.122368499

    authors: Tan CM,Wilson MH,MacMillan LB,Kobilka BK,Limbird LE

    更新日期:2002-09-17 00:00:00

  • Transcriptionally repressed genes become aberrantly methylated and distinguish tumors of different lineages in breast cancer.

    abstract::Aberrant promoter hypermethylation is frequently observed in cancer. The potential for this mechanism to contribute to tumor development depends on whether the genes affected are repressed because of their methylation. Many aberrantly methylated genes play important roles in development and are bivalently marked in ES...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1013224108

    authors: Sproul D,Nestor C,Culley J,Dickson JH,Dixon JM,Harrison DJ,Meehan RR,Sims AH,Ramsahoye BH

    更新日期:2011-03-15 00:00:00

  • Synergistic dual positive feedback loops established by molecular sequestration generate robust bimodal response.

    abstract::Feedback loops are ubiquitous features of biological networks and can produce significant phenotypic heterogeneity, including a bimodal distribution of gene expression across an isogenic cell population. In this work, a combination of experiments and computational modeling was used to explore the roles of multiple fee...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1211902109

    authors: Venturelli OS,El-Samad H,Murray RM

    更新日期:2012-11-27 00:00:00

  • NifEN-B complex of Azotobacter vinelandii is fully functional in nitrogenase FeMo cofactor assembly.

    abstract::Assembly of nitrogenase FeMoco is one of the key processes in bioinorganic chemistry. NifB and NifEN are two essential elements immediately adjacent to each other along the biosynthetic pathway of FeMoco. Previously, an 8Fe-precursor of FeMoco was identified on NifEN; however, the identity of the biosynthetic intermed...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1102773108

    authors: Wiig JA,Hu Y,Ribbe MW

    更新日期:2011-05-24 00:00:00

  • Extraocular muscle is defined by a fundamentally distinct gene expression profile.

    abstract::Skeletal muscle fibers are defined by patterned covariation of key traits that determine contractile and metabolic characteristics. Although the functional properties of most skeletal muscles result from their proportional content of a few conserved muscle fiber types, some, typically craniofacial, muscles exhibit fib...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.211257298

    authors: Porter JD,Khanna S,Kaminski HJ,Rao JS,Merriam AP,Richmonds CR,Leahy P,Li J,Andrade FH

    更新日期:2001-10-09 00:00:00

  • Muscle-regulated expression and determinants for neuromuscular junctional localization of the mouse RIalpha regulatory subunit of cAMP-dependent protein kinase.

    abstract::In skeletal muscle, transcription of the gene encoding the mouse type Ialpha (RIalpha) subunit of the cAMP-dependent protein kinase is initiated from the alternative noncoding first exons 1a and 1b. Here, we report that activity of the promoter upstream of exon 1a (Pa) depends on two adjacent E boxes (E1 and E2) in NI...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.081393598

    authors: Barradeau S,Imaizumi-Scherrer T,Weiss MC,Faust DM

    更新日期:2001-04-24 00:00:00

  • Cross-class metallo-β-lactamase inhibition by bisthiazolidines reveals multiple binding modes.

    abstract::Metallo-β-lactamases (MBLs) hydrolyze almost all β-lactam antibiotics and are unaffected by clinically available β-lactamase inhibitors (βLIs). Active-site architecture divides MBLs into three classes (B1, B2, and B3), complicating development of βLIs effective against all enzymes. Bisthiazolidines (BTZs) are carboxyl...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1601368113

    authors: Hinchliffe P,González MM,Mojica MF,González JM,Castillo V,Saiz C,Kosmopoulou M,Tooke CL,Llarrull LI,Mahler G,Bonomo RA,Vila AJ,Spencer J

    更新日期:2016-06-28 00:00:00

  • Frequency of molecular alterations affecting ras protooncogenes in human urinary tract tumors.

    abstract::Members of the ras gene family are activated as oncogenes in many different human cancers. To systematically determine the frequency at which such genes might be involved in the neoplastic process affecting a specific target tissue, urothelial cells, we surveyed a large series of urinary tract tumors for ras oncogenes...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.11.3849

    authors: Fujita J,Srivastava SK,Kraus MH,Rhim JS,Tronick SR,Aaronson SA

    更新日期:1985-06-01 00:00:00

  • Global analysis of stress-regulated mRNA turnover by using cDNA arrays.

    abstract::cDNA array technology has proven to be a powerful way to monitor global changes in gene expression patterns. Here, we present an approach that extends the current utility of cDNA arrays to allow the evaluation of the relative roles of transcription and mRNA turnover in governing gene expression on a global basis, comp...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.162212399

    authors: Fan J,Yang X,Wang W,Wood WH 3rd,Becker KG,Gorospe M

    更新日期:2002-08-06 00:00:00

  • ATP compartmentation in plastids and cytosol of Arabidopsis thaliana revealed by fluorescent protein sensing.

    abstract::Matching ATP:NADPH provision and consumption in the chloroplast is a prerequisite for efficient photosynthesis. In terms of ATP:NADPH ratio, the amount of ATP generated from the linear electron flow does not meet the demand of the Calvin-Benson-Bassham (CBB) cycle. Several different mechanisms to increase ATP availabi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1711497115

    authors: Voon CP,Guan X,Sun Y,Sahu A,Chan MN,Gardeström P,Wagner S,Fuchs P,Nietzel T,Versaw WK,Schwarzländer M,Lim BL

    更新日期:2018-11-06 00:00:00

  • Five computational developability guidelines for therapeutic antibody profiling.

    abstract::Therapeutic mAbs must not only bind to their target but must also be free from "developability issues" such as poor stability or high levels of aggregation. While small-molecule drug discovery benefits from Lipinski's rule of five to guide the selection of molecules with appropriate biophysical properties, there is cu...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1810576116

    authors: Raybould MIJ,Marks C,Krawczyk K,Taddese B,Nowak J,Lewis AP,Bujotzek A,Shi J,Deane CM

    更新日期:2019-03-05 00:00:00

  • Calcium-dependent copper redistributions in neuronal cells revealed by a fluorescent copper sensor and X-ray fluorescence microscopy.

    abstract::Dynamic fluxes of s-block metals like potassium, sodium, and calcium are of broad importance in cell signaling. In contrast, the concept of mobile transition metals triggered by cell activation remains insufficiently explored, in large part because metals like copper and iron are typically studied as static cellular n...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1009932108

    authors: Dodani SC,Domaille DW,Nam CI,Miller EW,Finney LA,Vogt S,Chang CJ

    更新日期:2011-04-12 00:00:00

  • The callipyge mutation enhances bidirectional long-range DLK1-GTL2 intergenic transcription in cis.

    abstract::The callipyge mutation (CLPG) is an A to G transition that affects a muscle-specific long-range control element located in the middle of the 90-kb DLK1-GTL2 intergenic (IG) region. It causes ectopic expression of a 327-kb cluster of imprinted genes in skeletal muscle, resulting in the callipyge muscular hypertrophy an...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0602844103

    authors: Takeda H,Caiment F,Smit M,Hiard S,Tordoir X,Cockett N,Georges M,Charlier C

    更新日期:2006-05-23 00:00:00

  • Developing dorsal root ganglion neurons require trophic support from their central processes: evidence for a role of retrogradely transported nerve growth factor from the central nervous system to the periphery.

    abstract::Injury to the peripheral processes produces a profound cell loss (40-50%) in the dorsal root ganglion of newborn rats. Although division of central processes produces little or no cellular change in sensory ganglion of adult animals, no information has been available on the effect of dorsal root section in developing ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.19.6245

    authors: Yip HK,Johnson EM Jr

    更新日期:1984-10-01 00:00:00

  • Mammalian multidrug-resistance gene: correlation of exon organization with structural domains and duplication of an ancestral gene.

    abstract::Analysis of the nucleotide and deduced amino acid sequences of the biologically active mouse mdr1 cDNA clone indicates that the protein is formed by two highly homologous halves, each containing six putative transmembrane domains and a nucleotide-binding site. The duplicated unit shows high sequence homology to the pr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.17.6488

    authors: Raymond M,Gros P

    更新日期:1989-09-01 00:00:00

  • Altered phase diagram due to a single point mutation in human gammaD-crystallin.

    abstract::The P23T mutant of human gammaD-crystallin (HGD) is associated with cataract. We have previously investigated the solution properties of this mutant, as well as those of the closely related P23V and P23S mutants, and shown that although mutations at site 23 of HGD do not produce a significant structural change in the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0707412104

    authors: McManus JJ,Lomakin A,Ogun O,Pande A,Basan M,Pande J,Benedek GB

    更新日期:2007-10-23 00:00:00

  • Load-dependent ADP binding to myosins V and VI: implications for subunit coordination and function.

    abstract::Dimeric myosins V and VI travel long distances in opposite directions along actin filaments in cells, taking multiple steps in a "hand-over-hand" fashion. The catalytic cycles of both myosins are limited by ADP dissociation, which is considered a key step in the walking mechanism of these motors. Here, we demonstrate ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0800564105

    authors: Oguchi Y,Mikhailenko SV,Ohki T,Olivares AO,De La Cruz EM,Ishiwata S

    更新日期:2008-06-03 00:00:00

  • Production of high-titer helper-free retroviruses by transient transfection.

    abstract::The generation of high-titer, helper-free retroviruses by transient transfection has been achieved by using the highly transfectable 293T cell line into which are stably introduced constructs that express retroviral packaging functions. The resulting ecotropic virus packaging cell line BOSC 23 produces infectious retr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.18.8392

    authors: Pear WS,Nolan GP,Scott ML,Baltimore D

    更新日期:1993-09-15 00:00:00

  • Ba2LnSbO6 and Sr2LnSbO6 (Ln = Dy, Ho, Gd) double perovskites: lanthanides in the geometrically frustrating fcc lattice.

    abstract::Magnetic ground states in solids often arise as a result of a delicate balance between competing factors. One currently active area of research in magnetic materials involves compounds in which long-range magnetic ordering at low temperatures is frustrated by the geometry of the crystalline lattice, a situation known ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0832394100

    authors: Karunadasa H,Huang Q,Ueland BG,Schiffer P,Cava RJ

    更新日期:2003-07-08 00:00:00

  • Copper- and copper-N-heterocyclic carbene-catalyzed C-H activating carboxylation of terminal alkynes with CO2 at ambient conditions.

    abstract::The use of carbon dioxide as a renewable and environmentally friendly source of carbon in organic synthesis is a highly attractive approach, but its real world applications remain a great challenge. The major obstacles for commercialization of most current protocols are their low catalytic performances, harsh reaction...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1010962107

    authors: Yu D,Zhang Y

    更新日期:2010-11-23 00:00:00

  • Functional differentiation of T cells in the intestine of T cell receptor transgenic mice.

    abstract::The intestinal lamina propria (LP) is a major effector site of the mucosal immune system where antigen-specific and antigen-nonspecific factors shape the functional responses of CD4+ T helper cells. To study the functional differentiation of LP T helper cells we utilized DO11.10 T cell receptor (TCR) transgenic (Tg) m...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.8.3920

    authors: Hurst SD,Sitterding SM,Ji S,Barrett TA

    更新日期:1997-04-15 00:00:00

  • Vitamin E reduces chromosomal damage and inhibits hepatic tumor formation in a transgenic mouse model.

    abstract::We have previously shown that chronic activation of mitogenic signaling induced by over-expression of c-myc and transforming growth factor-alpha (TGFalpha) transgenes in mouse liver induces a state of oxidative stress. We therefore proposed that increased reactive oxygen species (ROS) generation might be responsible f...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.040428797

    authors: Factor VM,Laskowska D,Jensen MR,Woitach JT,Popescu NC,Thorgeirsson SS

    更新日期:2000-02-29 00:00:00

  • M-current inhibition rapidly induces a unique CK2-dependent plasticity of the axon initial segment.

    abstract::Alterations in synaptic input, persisting for hours to days, elicit homeostatic plastic changes in the axon initial segment (AIS), which is pivotal for spike generation. Here, in hippocampal pyramidal neurons of both primary cultures and slices, we triggered a unique form of AIS plasticity by selectively targeting M-t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1708700114

    authors: Lezmy J,Lipinsky M,Khrapunsky Y,Patrich E,Shalom L,Peretz A,Fleidervish IA,Attali B

    更新日期:2017-11-21 00:00:00

  • Association of titin and myosin heavy chain in developing skeletal muscle.

    abstract::To understand molecular interactions that organize developing myofibrils, we examined the biosynthesis and interaction of titin and myosin heavy chain in cultures of developing muscle. Use of pulse-labeling, immunoprecipitation, and a reversible cross-linking procedure demonstrates that within minutes of synthesis, ti...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.16.7496

    authors: Isaacs WB,Kim IS,Struve A,Fulton AB

    更新日期:1992-08-15 00:00:00

  • Antibodies and IL-3 support helminth-induced basophil expansion.

    abstract::Basophils are powerful mediators of Th2 immunity and are present in increased numbers during allergic inflammation and helminth infection. Despite their ability to potentiate Th2 immunity the mechanisms regulating basophil development remain largely unknown. We have found a unique role for isotype-switched antibodies ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1117584109

    authors: Herbst T,Esser J,Prati M,Kulagin M,Stettler R,Zaiss MM,Hewitson JP,Merky P,Verbeek JS,Bourquin C,Camberis M,Prout M,Maizels RM,Le Gros G,Harris NL

    更新日期:2012-09-11 00:00:00

  • Ice-core evidence of abrupt climate changes.

    abstract::Ice-core records show that climate changes in the past have been large, rapid, and synchronous over broad areas extending into low latitudes, with less variability over historical times. These ice-core records come from high mountain glaciers and the polar regions, including small ice caps and the large ice sheets of ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.97.4.1331

    authors: Alley RB

    更新日期:2000-02-15 00:00:00