Functional evidence for active site location of tetrameric thymidylate synthase X at the interphase of three monomers.

Abstract:

:Little is known about the catalytic mechanism of the recently discovered ThyX family of flavin-dependent thymidylate synthases that are required for thymidylate (deoxythymidine 5'-monophosphate) synthesis in a large number of microbial species. Using a combination of site-directed mutagenesis and biochemical measurements, we have identified several residues of the Helicobacter pylori ThyX protein with crucial roles in ThyX catalysis. By providing functional evidence that the active site(s) of homotetrameric ThyX proteins is formed by three different subunits, our findings suggest that ThyX proteins have evolved through multimerization of inactive monomers. Moreover, because the active-site configurations of ThyX proteins, present in many human pathogenic bacteria, and of human thymidylate synthase ThyA are different, our results will aid in the identification of compounds specifically inhibiting microbial growth.

authors

Leduc D,Graziani S,Lipowski G,Marchand C,Le Maréchal P,Liebl U,Myllykallio H

doi

10.1073/pnas.0401365101

keywords:

subject

Has Abstract

pub_date

2004-05-11 00:00:00

pages

7252-7

issue

19

eissn

0027-8424

issn

1091-6490

pii

0401365101

journal_volume

101

pub_type

杂志文章
  • Aging and its relation to cell growth and differentiation in Drosophila imaginal discs: developmental response to growth restricting conditions.

    abstract::The development of Drosophila organ discs can be arrested by culturing them in adult male flies. These aged discs lose some of their differentiation competence and form incomplete imaginal structures. The more advanced the aging, the greater the loss of competence. Discs made to differentiate prematurely show deficien...

    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.72.11.4674

    authors: Schweizer P,Bodenstein D

    更新日期:1975-11-01 00:00:00

  • Nucleoporin MOS7/Nup88 is required for mitosis in gametogenesis and seed development in Arabidopsis.

    abstract::Angiosperm reproduction is characterized by alternate diploid sporophytic and haploid gametophytic generations. Gametogenesis shares similarities with that of animals except for the formation of the gametophyte, whereby haploid cells undergo several rounds of postmeiotic mitosis to form gametes and the accessory cells...

    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.1421911112

    authors: Park GT,Frost JM,Park JS,Kim TH,Lee JS,Oh SA,Twell D,Brooks JS,Fischer RL,Choi Y

    更新日期:2014-12-23 00:00:00

  • Comparative structural analysis of transcriptionally competent and incompetent rotavirus-antibody complexes.

    abstract::During genome transcription in rotavirus, as with many segmented double-stranded RNA viruses, mRNA is transcribed within the intact subviral particle and translocated through specific channels in the capsid. To understand how the conformation of the capsid affects the efficiency of transcriptional events in the viral ...

    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.96.10.5428

    authors: Lawton JA,Estes MK,Prasad BV

    更新日期:1999-05-11 00:00:00

  • Protein quantification across hundreds of experimental conditions.

    abstract::Quantitative studies of protein abundance rarely span more than a small number of experimental conditions and replicates. In contrast, quantitative studies of transcript abundance often span hundreds of experimental conditions and replicates. This situation exists, in part, because extracting quantitative data from la...

    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.0904100106

    authors: Khan Z,Bloom JS,Garcia BA,Singh M,Kruglyak L

    更新日期:2009-09-15 00:00:00

  • Active transport of calcium in inverted membrane vesicles of Escherichia coli.

    abstract::Accumulation of (45)Ca(++) was found to occur in membrane vesicles of E. coli prepared by lysis with a French pressure cell. The uptake occurs by active transport, requiring an energy source. Substrates of the electron transport chain, including D-lactate, reduced phenazine methosulfate, and NADH, stimulated accumulat...

    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.71.12.5042

    authors: Rosen BP,McClees JS

    更新日期:1974-12-01 00:00:00

  • Positive regulatory role of strigolactone in plant responses to drought and salt stress.

    abstract::This report provides direct evidence that strigolactone (SL) positively regulates drought and high salinity responses in Arabidopsis. Both SL-deficient and SL-response [more axillary growth (max)] mutants exhibited hypersensitivity to drought and salt stress, which was associated with shoot- rather than root-related 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.1322135111

    authors: Ha CV,Leyva-González MA,Osakabe Y,Tran UT,Nishiyama R,Watanabe Y,Tanaka M,Seki M,Yamaguchi S,Dong NV,Yamaguchi-Shinozaki K,Shinozaki K,Herrera-Estrella L,Tran LS

    更新日期:2014-01-14 00:00:00

  • Anatoxin-a interactions with cholinergic synaptic molecules.

    abstract::Anatoxin-a, a bicyclic amine isolated from blue-green alga, binds to the nicotinic acetylcholine receptor of Torpedo electric tissue, thereby inducing conformational changes in the postsynaptic receptor--ion channel complex as evidenced by alterations in the binding of radiolabeled ligands to the complex. Anatoxin-a b...

    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.78.7.4639

    authors: Aronstam RS,Witkop B

    更新日期:1981-07-01 00:00:00

  • Structural insight into distinct mechanisms of protease inhibition by antibodies.

    abstract::To better understand how the relatively flat antigen-combining sites of antibodies interact with the concave shaped substrate-binding clefts of proteases, we determined the structures of two antibodies in complex with the trypsin-like hepatocyte growth-factor activator (HGFA). The two inhibitory antibodies, Ab58 and 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.0708251104

    authors: Wu Y,Eigenbrot C,Liang WC,Stawicki S,Shia S,Fan B,Ganesan R,Lipari MT,Kirchhofer D

    更新日期:2007-12-11 00:00:00

  • Coincidence cloning of Alu PCR products.

    abstract::Coincidence cloning allows the isolation of sequences held in common by two genomic DNA populations. Human DNA from two human-hamster hybrid cell lines was amplified by Alu-repeat primers (Alu PCR) and the products originating from the shared human chromosomal region were cloned. To achieve this, human sequences were ...

    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.88.15.6765

    authors: Aslanidis C,de Jong PJ

    更新日期:1991-08-01 00:00:00

  • Shaping a bacterial genome by large chromosomal replacements, the evolutionary history of Streptococcus agalactiae.

    abstract::Bacterial populations are subject to complex processes of diversification that involve mutation and horizontal DNA transfer mediated by transformation, transduction, or conjugation. Tracing the evolutionary events leading to genetic changes allows us to infer the history of a microbe. Here, we combine experimental and...

    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.0803654105

    authors: Brochet M,Rusniok C,Couvé E,Dramsi S,Poyart C,Trieu-Cuot P,Kunst F,Glaser P

    更新日期:2008-10-14 00:00:00

  • Molecular cloning and primary structure of human glial fibrillary acidic protein.

    abstract::Glial fibrillary acidic protein (GFAP) is an intermediate-filament (IF) protein that is highly specific for cells of astroglial lineage, although its tissue-specific role is speculative. Determination of the primary structure of this protein should be of importance for understanding the functional role it plays in ast...

    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.86.13.5178

    authors: Reeves SA,Helman LJ,Allison A,Israel MA

    更新日期:1989-07-01 00:00:00

  • Independent and combined analyses of sequences from all three genomic compartments converge on the root of flowering plant phylogeny.

    abstract::Plant phylogenetic estimates are most likely to be reliable when congruent evidence is obtained independently from the mitochondrial, plastid, and nuclear genomes with all methods of analysis. Here, results are presented from separate and combined genomic analyses of new and previously published data, including six 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.220427497

    authors: Barkman TJ,Chenery G,McNeal JR,Lyons-Weiler J,Ellisens WJ,Moore G,Wolfe AD,dePamphilis CW

    更新日期:2000-11-21 00:00:00

  • Initiation factor IF-3-dependent binding of Escherichia coli ribosomes and N-formylmethionine transfer-RNA to rabbit globin messenger.

    abstract::An initiation complex has been formed in high yields from E. coli ribosomes, 9S messenger RNA for rabbit hemoglobin, and N-formylmethionine-tRNA. Initiation factor IF-3 is required for the binding and puromycin is required for the release of fMet. Valyl-tRNA fails to bind to the second codon, whereas a mixture of 15 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.69.7.1843

    authors: Noll M,Noll H,Lingrel JB

    更新日期:1972-07-01 00:00:00

  • Cell density regulates cellular reversal frequency in Myxococcus xanthus.

    abstract::Myxococcus xanthus is a Gram-negative bacterium that aggregates to form fruiting bodies when nutrients are limiting. Previous studies showed that the frz mutants that are defective in chemotaxis exhibited irregular and infrequent patterns of cellular reversal. In contrast, wild-type cells, when examined individually, ...

    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.93.9.4142

    authors: Shi W,Ngok FK,Zusman DR

    更新日期:1996-04-30 00:00:00

  • Dynamic subunit stoichiometry confers a progressive continuum of pharmacological sensitivity by KCNQ potassium channels.

    abstract::Voltage-gated KCNQ1 (Kv7.1) potassium channels are expressed abundantly in heart but they are also found in multiple other tissues. Differential coassembly with single transmembrane KCNE beta subunits in different cell types gives rise to a variety of biophysical properties, hence endowing distinct physiological roles...

    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.1300684110

    authors: Yu H,Lin Z,Mattmann ME,Zou B,Terrenoire C,Zhang H,Wu M,McManus OB,Kass RS,Lindsley CW,Hopkins CR,Li M

    更新日期:2013-05-21 00:00:00

  • Purification of replication protein C, a cellular protein involved in the initial stages of simian virus 40 DNA replication in vitro.

    abstract::The replication of simian virus 40 (SV40) DNA is dependent upon a single viral protein [tumor (T) antigen] and multiple cellular proteins. To define the required cellular proteins, we have made use of a cell-free system that supports the replication of plasmid DNA molecules containing the SV40 origin of replication. W...

    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.86.10.3584

    authors: Virshup DM,Kelly TJ

    更新日期:1989-05-01 00:00:00

  • Higher offspring survival among Tibetan women with high oxygen saturation genotypes residing at 4,000 m.

    abstract::Here we test the hypothesis that high-altitude native resident Tibetan women with genotypes for high oxygen saturation of hemoglobin, and thus less physiological hypoxic stress, have higher Darwinian fitness than women with low oxygen saturation genotypes. Oxygen saturation and genealogical data were collected from re...

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

    pub_type: 杂志文章,多中心研究

    doi:10.1073/pnas.0405949101

    authors: Beall CM,Song K,Elston RC,Goldstein MC

    更新日期:2004-09-28 00:00:00

  • Mutations in the telomerase component NHP2 cause the premature ageing syndrome dyskeratosis congenita.

    abstract::Dyskeratosis congenita is a premature aging syndrome characterized by muco-cutaneous features and a range of other abnormalities, including early greying, dental loss, osteoporosis, and malignancy. Dyskeratosis congenita cells age prematurely and have very short telomeres. Patients have mutations in genes that encode ...

    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.0800042105

    authors: Vulliamy T,Beswick R,Kirwan M,Marrone A,Digweed M,Walne A,Dokal I

    更新日期:2008-06-10 00:00:00

  • Extensive and specific responses of a eukaryote to bacterial quorum-sensing signals.

    abstract::Many bacteria use N-acyl homoserine lactone (AHL) signals to coordinate the behavior of individual cells in a local population. The successful infection of eukaryotic hosts by bacteria seems to depend particularly on such AHL-mediated "quorum-sensing" regulation. We have used proteome analysis to show that a eukaryoti...

    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.262672599

    authors: Mathesius U,Mulders S,Gao M,Teplitski M,Caetano-Anolles G,Rolfe BG,Bauer WD

    更新日期:2003-02-04 00:00:00

  • RNA-binding protein Sam68 controls synapse number and local β-actin mRNA metabolism in dendrites.

    abstract::Proper synaptic function requires the spatial and temporal compartmentalization of RNA metabolism via transacting RNA-binding proteins (RBPs). Loss of RBP activity leads to abnormal posttranscriptional regulation and results in diverse neurological disorders with underlying deficits in synaptic morphology and transmis...

    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.1209811110

    authors: Klein ME,Younts TJ,Castillo PE,Jordan BA

    更新日期:2013-02-19 00:00:00

  • Behavior-specific changes in transcriptional modules lead to distinct and predictable neurogenomic states.

    abstract::Using brain transcriptomic profiles from 853 individual honey bees exhibiting 48 distinct behavioral phenotypes in naturalistic contexts, we report that behavior-specific neurogenomic states can be inferred from the coordinated action of transcription factors (TFs) and their predicted target genes. Unsupervised hierar...

    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.1114093108

    authors: Chandrasekaran S,Ament SA,Eddy JA,Rodriguez-Zas SL,Schatz BR,Price ND,Robinson GE

    更新日期:2011-11-01 00:00:00

  • Regulation of cyclic and linear electron flow in higher plants.

    abstract::Cyclic electron flow is increasingly recognized as being essential in plant growth, generating a pH gradient across thylakoid membrane (ΔpH) that contributes to ATP synthesis and triggers the protective process of nonphotochemical quenching (NPQ) under stress conditions. Here, we report experiments demonstrating the i...

    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.1110189108

    authors: Joliot P,Johnson GN

    更新日期:2011-08-09 00:00:00

  • Varicella-zoster virus infection of human dorsal root ganglia in vivo.

    abstract::Varicella-zoster virus (VZV) causes varicella and establishes latency in sensory ganglia. VZV reactivation results in herpes zoster. We developed a model using human dorsal root ganglion (DRG) xenografts in severe combined immunodeficient (SCID) mice to investigate VZV infection of differentiated neurons and satellite...

    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.0501045102

    authors: Zerboni L,Ku CC,Jones CD,Zehnder JL,Arvin AM

    更新日期:2005-05-03 00:00:00

  • The displacement field associated with the freezing of a melt and its role in determining crystal growth kinetics.

    abstract::The atomic displacements associated with the freezing of metals and salts are calculated by treating crystal growth as an assignment problem through the use of an optimal transport algorithm. Converting these displacements into timescales based on the dynamics of the bulk liquid, we show that we can predict the activa...

    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.1915806117

    authors: Sun G,Hawken A,Harrowell P

    更新日期:2020-02-18 00:00:00

  • Kinetic analysis of a complete poxvirus transcriptome reveals an immediate-early class of genes.

    abstract::Vaccinia virus is the prototypic orthopoxvirus and was the vaccine used to eradicate smallpox, yet the expression profiles of many of its genes remain unknown. Using a genome tiling array approach, we simultaneously measured the expression levels of all 223 annotated vaccinia virus genes during infection and determine...

    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.0711573105

    authors: Assarsson E,Greenbaum JA,Sundström M,Schaffer L,Hammond JA,Pasquetto V,Oseroff C,Hendrickson RC,Lefkowitz EJ,Tscharke DC,Sidney J,Grey HM,Head SR,Peters B,Sette A

    更新日期:2008-02-12 00:00:00

  • Antibody-induced uncoating of human rhinovirus B14.

    abstract::Rhinoviruses (RVs) are the major causes of common colds in humans. They have a nonenveloped, icosahedral capsid surrounding a positive-strand RNA genome. Here we report that the antigen-binding (Fab) fragment of a neutralizing antibody (C5) can trigger genome release from RV-B14 to form emptied particles and neutraliz...

    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.1707369114

    authors: Dong Y,Liu Y,Jiang W,Smith TJ,Xu Z,Rossmann MG

    更新日期:2017-07-25 00:00:00

  • Molecular cloning of complementary DNAs encoding two cationic peroxidases from cultivated peanut cells.

    abstract::We have isolated, cloned, and characterized two cDNAs corresponding to the mRNAs for cationic peroxidases synthesized by cultured peanut cells. The first clone was obtained from a phage lambda gt11 library screened with antibodies directed against the major secreted isozyme. Its predicted amino acid sequence, deduced ...

    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.87.22.8874

    authors: Buffard D,Breda C,van Huystee RB,Asemota O,Pierre M,Ha DB,Esnault R

    更新日期:1990-11-01 00:00:00

  • Oncogenic transformation induced by the p110beta, -gamma, and -delta isoforms of class I phosphoinositide 3-kinase.

    abstract::Class I phosphoinositide 3-kinase contains four isoforms of the catalytic subunit, p110alpha, -beta, -gamma, and -delta. At physiological levels of expression, the wild-type p110alpha isoform lacks oncogenic potential, but gain-of-function mutations and overexpression of p110alpha are correlated with oncogenicity. 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.0510772103

    authors: Kang S,Denley A,Vanhaesebroeck B,Vogt PK

    更新日期:2006-01-31 00:00:00

  • Noncanonical SMC protein in Mycobacterium smegmatis restricts maintenance of Mycobacterium fortuitum plasmids.

    abstract::Research on tuberculosis and leprosy was revolutionized by the development of a plasmid transformation system in the fast-growing surrogate, Mycobacterium smegmatis. This transformation system was made possible by the successful isolation of a M. smegmatis mutant strain mc(2)155, whose efficient plasmid transformation...

    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.1414207111

    authors: Panas MW,Jain P,Yang H,Mitra S,Biswas D,Wattam AR,Letvin NL,Jacobs WR Jr

    更新日期:2014-09-16 00:00:00

  • A receptor model for tumor promoters: rational superposition of teleocidins and phorbol esters.

    abstract::Four 12-O-tetradecanoyl-13-O-acetylphorbol-type tumor promoters--teleocidin, phorbol ester, aplysiatoxin, and ingenol ester--are superposed in an attempt to understand their common biological activity on the assumption that they may bind to the same receptor site. A method using three-dimensional computer graphics was...

    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.85.11.3688

    authors: Itai A,Kato Y,Tomioka N,Iitaka Y,Endo Y,Hasegawa M,Shudo K,Fujiki H,Sakai S

    更新日期:1988-06-01 00:00:00