Two-dimensional infrared spectra reveal relaxation of the nonnucleoside inhibitor TMC278 complexed with HIV-1 reverse transcriptase.

Abstract:

:The two nitrile groups at the wings of the nonnucleoside HIV-1 reverse transcriptase (RT) inhibitor TMC278 are both identified in high-sensitivity 2D IR spectroscopy experiments of the HIV-1 RT/TMC278 complex. The vibrational spectra indicate that the two arms of the inhibitor sense quite different environments within the hydrophobic pocket. The vibrational relaxation of the two arms are almost equal at 3 ps from model studies. The 2D IR spectra expose a significant distribution of nitrile frequencies that diffuse at equilibrium on ultrafast time scales ranging from hundreds of femtoseconds to tens of picoseconds. The slow spectral diffusion of the cyanovinyl arm of the inhibitor is attributed to its interaction with the backbone and side chains in the hydrophobic tunnel. The results show that the inhibitor cyano modes lose memory of their structural configurations relative to the hydrophobic pocket within tens of picoseconds. The cross-peaks between the two arms of the drug are tentatively attributed to relaxation of the nitrile state with both arms excited.

authors

Fang C,Bauman JD,Das K,Remorino A,Arnold E,Hochstrasser RM

doi

10.1073/pnas.0709320104

subject

Has Abstract

pub_date

2008-02-05 00:00:00

pages

1472-7

issue

5

eissn

0027-8424

issn

1091-6490

pii

0709320104

journal_volume

105

pub_type

杂志文章
  • The structure of zetekitoxin AB, a saxitoxin analog from the Panamanian golden frog Atelopus zeteki: a potent sodium-channel blocker.

    abstract::Bufonid anurans of the genus Atelopus contain both steroidal bufadienolides and various guanidinium alkaloids of the tetrodotoxin class. The former inhibit sodium-potassium ATPases, whereas the latter block voltage-dependent sodium channels. The structure of one guanidinium alkaloid, zetekitoxin AB, has remained a mys...

    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.0400368101

    authors: Yotsu-Yamashita M,Kim YH,Dudley SC Jr,Choudhary G,Pfahnl A,Oshima Y,Daly JW

    更新日期:2004-03-30 00:00:00

  • Interisland and interarchipelago transfer of stone tools in prehistoric Polynesia.

    abstract::Tracing interisland and interarchipelago movements of people and artifacts in prehistoric Polynesia has posed a challenge to archaeologists due to the lack of pottery and obsidian, two materials most readily used in studies of prehistoric trade or exchange. Here we report the application of nondestructive energy-dispe...

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

    pub_type: 历史文章,杂志文章

    doi:10.1073/pnas.93.4.1381

    authors: Weisler MI,Kirch PV

    更新日期:1996-02-20 00:00:00

  • Detection of proopiomelanocortin mRNA by in situ hybridization with an oligonucleotide probe.

    abstract::Synthetic oligonucleotide probes can be easily obtained and used, in contrast to cDNA cloning to develop probes, and thus the present study was carried out to determine whether such probes could also be useful for in situ hybridization. A 24-base synthetic oligonucleotide complementary to part of the alpha-melanocyte-...

    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.83.15.5419

    authors: Lewis ME,Sherman TG,Burke S,Akil H,Davis LG,Arentzen R,Watson SJ

    更新日期:1986-08-01 00:00:00

  • Brain-specific deletion of neuropathy target esterase/swisscheese results in neurodegeneration.

    abstract::Neuropathy target esterase (NTE) is a neuronal membrane protein originally identified for its property to be modified by organo-phosphates (OPs), which in humans cause neuropathy characterized by axonal degeneration. Drosophila mutants for the homolog gene of NTE, swisscheese (sws), indicated a possible involvement 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.0401030101

    authors: Akassoglou K,Malester B,Xu J,Tessarollo L,Rosenbluth J,Chao MV

    更新日期:2004-04-06 00:00:00

  • Self-association of gene-32 protein of bacteriophage T4.

    abstract::The self-association of gene-32 protein has been studied by sedimentation equilibrium centrifugation and polyacrylamide gel electrophoresis, in order to better understand its role in DNA replication and genetic recombination. The monomer molecular weight of gene-32 protein is 38,000 in guanidine hydrochloride and 34,0...

    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.69.9.2741

    authors: Carroll RB,Neet KE,Goldthwait DA

    更新日期:1972-09-01 00:00:00

  • Interaction of Staphylococcus aureus toxin "superantigens" with human T cells.

    abstract::A modification of the polymerase chain reaction has been used to establish the fact that a collection of Staphylococcus aureus toxins are "superantigens," each of which interacts with the T-cell alpha beta receptor of human T cells by means of a specific set of V beta elements. ...

    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.86.22.8941

    authors: Choi YW,Kotzin B,Herron L,Callahan J,Marrack P,Kappler J

    更新日期:1989-11-01 00:00:00

  • Large seasonal swings in leaf area of Amazon rainforests.

    abstract::Despite early speculation to the contrary, all tropical forests studied to date display seasonal variations in the presence of new leaves, flowers, and fruits. Past studies were focused on the timing of phenological events and their cues but not on the accompanying changes in leaf area that regulate vegetation-atmosph...

    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.0611338104

    authors: Myneni RB,Yang W,Nemani RR,Huete AR,Dickinson RE,Knyazikhin Y,Didan K,Fu R,Negrón Juárez RI,Saatchi SS,Hashimoto H,Ichii K,Shabanov NV,Tan B,Ratana P,Privette JL,Morisette JT,Vermote EF,Roy DP,Wolfe RE,Friedl MA,

    更新日期:2007-03-20 00:00:00

  • Lactobacillus reuteri-produced cyclic dipeptides quench agr-mediated expression of toxic shock syndrome toxin-1 in staphylococci.

    abstract::The production of the staphylococcal exotoxin toxic shock syndrome toxin-1 (TSST-1) by Staphylococcus aureus has been associated with essentially all cases of menstruation-associated toxic shock syndrome (TSS). In this work, we show that the human vaginal isolate Lactobacillus reuteri RC-14 produces small signaling mo...

    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.1017431108

    authors: Li J,Wang W,Xu SX,Magarvey NA,McCormick JK

    更新日期:2011-02-22 00:00:00

  • Membrane-associated immunoglobulin of rabbit peripheral blood lymphocytes: allelic exclusion at the b locus.

    abstract::Light chain allotypic determinants were demonstrated on the surface of peripheral blood lymphocytes of rabbits. By means of a combined immunofluorescent and autoradiographic technique, a great majority of the individual lymphocytes of rabbits heteroxygous at the b locus were shown to have detectable quantities of only...

    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.68.2.430

    authors: Davie JM,Paul WE,Mage RG,Goldman MB

    更新日期:1971-02-01 00:00:00

  • Nonconscious activation of placebo and nocebo pain responses.

    abstract::The dominant theories of human placebo effects rely on a notion that consciously perceptible cues, such as verbal information or distinct stimuli in classical conditioning, provide signals that activate placebo effects. However, growing evidence suggest that behavior can be triggered by stimuli presented outside of co...

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

    pub_type: 杂志文章,随机对照试验

    doi:10.1073/pnas.1202056109

    authors: Jensen KB,Kaptchuk TJ,Kirsch I,Raicek J,Lindstrom KM,Berna C,Gollub RL,Ingvar M,Kong J

    更新日期:2012-09-25 00:00:00

  • Human cytomegalovirus latency alters the cellular secretome, inducing cluster of differentiation (CD)4+ T-cell migration and suppression of effector function.

    abstract::After primary infection, human cytomegalovirus (HCMV) persists as a life-long latent infection, with host immunosuppression often resulting in clinical reactivation. During lytic infection, major changes in the expression of secreted cellular proteins (the secretome) occur that have profound effects on host-cell inter...

    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.1204836109

    authors: Mason GM,Poole E,Sissons JG,Wills MR,Sinclair JH

    更新日期:2012-09-04 00:00:00

  • Brain-wide structural and functional disruption in mice with oligodendrocyte-specific Nf1 deletion is rescued by inhibition of nitric oxide synthase.

    abstract::Neurofibromin gene (NF1) mutation causes neurofibromatosis type 1 (NF1), a disorder in which brain white matter deficits identified by neuroimaging are common, yet of unknown cellular etiology. In mice, Nf1 loss in adult oligodendrocytes causes myelin decompaction and increases oligodendrocyte nitric oxide (NO) levels...

    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.2008391117

    authors: Asleh J,Shofty B,Cohen N,Kavushansky A,López-Juárez A,Constantini S,Ratner N,Kahn I

    更新日期:2020-09-08 00:00:00

  • On the molecular mechanisms of transposition.

    abstract::We present a model for transposition that allows a choice between cointegrate formation (replicon fusion) and direct transposition. We propose that initiation of the process occurs by invasion of the target DNA by a single-stranded end of the transposable element. This leads to nicking of one of the DNA strands of 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.78.8.4858

    authors: Galas DJ,Chandler M

    更新日期:1981-08-01 00:00:00

  • Tyrosine kinase JAK1 is associated with the granulocyte-colony-stimulating factor receptor and both become tyrosine-phosphorylated after receptor activation.

    abstract::Granulocyte-colony-stimulating factor (G-CSF) stimulates the proliferation and differentiation of cells of the neutrophil lineage by interaction with a specific receptor. Early signal transduction events following G-CSF receptor activation were studied. We detected tyrosine phosphorylation of both the G-CSF receptor a...

    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.91.8.2985

    authors: Nicholson SE,Oates AC,Harpur AG,Ziemiecki A,Wilks AF,Layton JE

    更新日期:1994-04-12 00:00:00

  • Older mothers produce more successful daughters.

    abstract::Annual reproductive success and senescence patterns vary substantially among individuals in the wild. However, it is still seldom considered that senescence may not only affect an individual but also affect age-specific reproductive success in its offspring, generating transgenerational reproductive senescence. We use...

    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.1908551117

    authors: Kroeger SB,Blumstein DT,Armitage KB,Reid JM,Martin JGA

    更新日期:2020-03-03 00:00:00

  • beta 2 nicotinic acetylcholine receptor subunit modulates protective responses to stress: A receptor basis for sleep-disordered breathing after nicotine exposure.

    abstract::Nicotine exposure diminishes the protective breathing and arousal responses to stress (hypoxia). By exacerbating sleep-disordered breathing, this disturbance could underpin the well established association between smoking and the increased risk of sudden infant death syndrome. We show here that the protective 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.192463599

    authors: Cohen G,Han ZY,Grailhe R,Gallego J,Gaultier C,Changeux JP,Lagercrantz H

    更新日期:2002-10-01 00:00:00

  • Neisseria gonorrhoeae-derived heptose elicits an innate immune response and drives HIV-1 expression.

    abstract::Clinical and epidemiological synergy exists between the globally important sexually transmitted infections, gonorrhea and HIV. Neisseria gonorrhoeae, which causes gonorrhea, is particularly adept at driving HIV-1 expression, but the molecular determinants of this relationship remain undefined. N. gonorrhoeae liberates...

    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.1303738110

    authors: Malott RJ,Keller BO,Gaudet RG,McCaw SE,Lai CC,Dobson-Belaire WN,Hobbs JL,St Michael F,Cox AD,Moraes TF,Gray-Owen SD

    更新日期:2013-06-18 00:00:00

  • Early onset preeclampsia in a model for human placental trophoblast.

    abstract::We describe a model for early onset preeclampsia (EOPE) that uses induced pluripotent stem cells (iPSCs) generated from umbilical cords of EOPE and control (CTL) pregnancies. These iPSCs were then converted to placental trophoblast (TB) representative of early pregnancy. Marker gene analysis indicated that both sets o...

    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.1816150116

    authors: Sheridan MA,Yang Y,Jain A,Lyons AS,Yang P,Brahmasani SR,Dai A,Tian Y,Ellersieck MR,Tuteja G,Schust DJ,Schulz LC,Ezashi T,Roberts RM

    更新日期:2019-03-05 00:00:00

  • Chemical and mechanical stimuli act on common signal transduction and cytoskeletal networks.

    abstract::Signal transduction pathways activated by chemoattractants have been extensively studied, but little is known about the events mediating responses to mechanical stimuli. We discovered that acute mechanical perturbation of cells triggered transient activation of all tested components of the chemotactic signal transduct...

    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.1608767113

    authors: Artemenko Y,Axiotakis L Jr,Borleis J,Iglesias PA,Devreotes PN

    更新日期:2016-11-22 00:00:00

  • Early experience in humans is associated with changes in neuropeptides critical for regulating social behavior.

    abstract::The formation of social attachments is a critical component of human relationships. Infants begin to bond to their caregivers from the moment of birth, and these social bonds continue to provide regulatory emotional functions throughout adulthood. It is difficult to examine the interactions between social experience a...

    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.0504767102

    authors: Wismer Fries AB,Ziegler TE,Kurian JR,Jacoris S,Pollak SD

    更新日期:2005-11-22 00:00:00

  • Correlation of enterohemorrhagic Escherichia coli O157 prevalence in feces, hides, and carcasses of beef cattle during processing.

    abstract::A survey was performed to estimate the frequency of enterohemorrhagic Escherichia coli O157:H7 or O157:nonmotile (EHEC O157) in feces and on hides within groups of fed cattle from single sources (lots) presented for slaughter at meat processing plants in the Midwestern United States, as well as frequency of carcass co...

    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.060024897

    authors: Elder RO,Keen JE,Siragusa GR,Barkocy-Gallagher GA,Koohmaraie M,Laegreid WW

    更新日期:2000-03-28 00:00:00

  • Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors.

    abstract::Rapid and efficient protocols to generate oligodendrocytes (OL) from human induced pluripotent stem cells (iPSC) are currently lacking, but may be a key technology to understand the biology of myelin diseases and to develop treatments for such disorders. Here, we demonstrate that the induction of three transcription 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.1614412114

    authors: Ehrlich M,Mozafari S,Glatza M,Starost L,Velychko S,Hallmann AL,Cui QL,Schambach A,Kim KP,Bachelin C,Marteyn A,Hargus G,Johnson RM,Antel J,Sterneckert J,Zaehres H,Schöler HR,Baron-Van Evercooren A,Kuhlmann T

    更新日期:2017-03-14 00:00:00

  • Novel use of synthetic oligonucleotide insertion mutants for the study of homologous recombination in mammalian cells.

    abstract::Thymidine kinase-deficient mouse L cells have been transformed with plasmid DNAs carrying 8-base-pair Xho I linker insertion mutations in the coding region of the herpes simplex virus type 1 thymidine kinase gene. When the mutant plasmids are introduced individually into LTK- cells, transformation efficiencies are gre...

    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.80.15.4827

    authors: Shapira G,Stachelek JL,Letsou A,Soodak LK,Liskay RM

    更新日期:1983-08-01 00:00:00

  • Diverse conjugative elements silence natural transformation in Legionella species.

    abstract::Natural transformation (i.e., the uptake of DNA and its stable integration in the chromosome) is a major mechanism of horizontal gene transfer in bacteria. Although the vast majority of bacterial genomes carry the genes involved in natural transformation, close relatives of naturally transformable species often appear...

    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.1909374116

    authors: Durieux I,Ginevra C,Attaiech L,Picq K,Juan PA,Jarraud S,Charpentier X

    更新日期:2019-09-10 00:00:00

  • Partial amino-acid sequence of NAD-specific glutamate dehydrogenase of Neurospora crassa.

    abstract::Parts of the primary structure of the NAD-specific glutamate dehydrogenase [L-glutamate:NAD oxidoreductase (deaminating), EC 1.4.1.2] from Neurospora crassa are presented. Segments of the sequence representing 886 unique amino-acid residues have been determined; the largest contains 267 residues. There are only short ...

    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.72.12.4891

    authors: Austen BM,Nyc JF,Degani Y,Smith EL

    更新日期:1975-12-01 00:00:00

  • Antigen induces chronic idiotype suppression.

    abstract::Hapten coupled to isologous gamma globulin can substitute for anti-idiotypic antibody in the induction of neonatal chronic idiotype suppression. The immunologically suppressed animals fail to express an idiotypically defined subset of anti-hapten antibodies in later life and harbor regulatory T cells that prevent 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.82.12.4217

    authors: Tokuhisa T,Rajewsky K

    更新日期:1985-06-01 00:00:00

  • Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle.

    abstract::Recent studies have shown that genes involved in oxidative phosphorylation (OXPHOS) exhibit reduced expression in skeletal muscle of diabetic and prediabetic humans. Moreover, these changes may be mediated by the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alph...

    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.0401401101

    authors: Mootha VK,Handschin C,Arlow D,Xie X,St Pierre J,Sihag S,Yang W,Altshuler D,Puigserver P,Patterson N,Willy PJ,Schulman IG,Heyman RA,Lander ES,Spiegelman BM

    更新日期:2004-04-27 00:00:00

  • Substitution rate comparisons between grasses and palms: synonymous rate differences at the nuclear gene Adh parallel rate differences at the plastid gene rbcL.

    abstract::A number of studies have noted that nucleotide substitution rates at the chloroplast-encoded rbcL locus violate the molecular clock principle. Substitution rate variation at this plastid gene is particularly pronounced between palms and grasses; for example, a previous study estimated that substitution rates in rbcL s...

    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.93.19.10274

    authors: Gaut BS,Morton BR,McCaig BC,Clegg MT

    更新日期:1996-09-17 00:00:00

  • Splicing inhibition of U2AF65 leads to alternative exon skipping.

    abstract::U2 snRNP auxiliary factor 65 kDa (U2AF(65)) is a general splicing factor that contacts polypyrimidine (Py) tract and promotes prespliceosome assembly. In this report, we show that U2AF(65) stimulates alternative exon skipping in spinal muscular atrophy (SMA)-related survival motor neuron (SMN) pre-mRNA. A stronger 5' ...

    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.1500639112

    authors: Cho S,Moon H,Loh TJ,Jang HN,Liu Y,Zhou J,Ohn T,Zheng X,Shen H

    更新日期:2015-08-11 00:00:00

  • Sympatric speciation revealed by genome-wide divergence in the blind mole rat Spalax.

    abstract::Sympatric speciation (SS), i.e., speciation within a freely breeding population or in contiguous populations, was first proposed by Darwin [Darwin C (1859) On the Origins of Species by Means of Natural Selection] and is still controversial despite theoretical support [Gavrilets S (2004) Fitness Landscapes and the Orig...

    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.1514896112

    authors: Li K,Hong W,Jiao H,Wang GD,Rodriguez KA,Buffenstein R,Zhao Y,Nevo E,Zhao H

    更新日期:2015-09-22 00:00:00