The crystal structure of Pyrococcus furiosus ornithine carbamoyltransferase reveals a key role for oligomerization in enzyme stability at extremely high temperatures.

Abstract:

:The Pyrococcus furiosus (PF) ornithine carbamoyltransferase (OTCase; EC 2.1.3.3) is an extremely heat-stable enzyme that maintains about 50% of its activity after heat treatment for 60 min at 100 degrees C. To understand the molecular basis of thermostability of this enzyme, we have determined its three-dimensional structure at a resolution of 2.7 A and compared it with the previously reported structures of OTCases isolated from mesophilic bacteria. Most OTCases investigated up to now are homotrimeric and devoid of allosteric properties. A striking exception is the catabolic OTCase from Pseudomonas aeruginosa, which is allosterically regulated and built up of four trimers disposed in a tetrahedral manner, an architecture that actually underlies the allostery of the enzyme. We now report that the thermostable PF OTCase (420 kDa) presents the same 23-point group symmetry. The enzyme displays Michaelis-Menten kinetics. A detailed comparison of the two enzymes suggests that, in OTCases, not only allostery but also thermophily was achieved through oligomerization of a trimer as a common catalytic motif. Thermal stabilization of the PF OTCase dodecamer is mainly the result of hydrophobic interfaces between trimers, at positions where allosteric binding sites have been identified in the allosteric enzyme. The present crystallographic analysis of PF OTCase provides a structural illustration that oligomerization can play a major role in extreme thermal stabilization.

authors

Villeret V,Clantin B,Tricot C,Legrain C,Roovers M,Stalon V,Glansdorff N,Van Beeumen J

doi

10.1073/pnas.95.6.2801

subject

Has Abstract

pub_date

1998-03-17 00:00:00

pages

2801-6

issue

6

eissn

0027-8424

issn

1091-6490

journal_volume

95

pub_type

杂志文章
  • Genetically modified anthrax lethal toxin safely delivers whole HIV protein antigens into the cytosol to induce T cell immunity.

    abstract::Bacillus anthrax lethal toxin can be engineered to deliver foreign proteins to the cytosol for antigen presentation to CD8 T cells. Vaccination with modified toxins carrying 8-9 amino acid peptide epitopes induces protective immunity in mice. To evaluate whether large protein antigens can be used with this system, rec...

    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.97.14.8027

    authors: Lu Y,Friedman R,Kushner N,Doling A,Thomas L,Touzjian N,Starnbach M,Lieberman J

    更新日期:2000-07-05 00:00:00

  • Generalized random fields related to self-intersections of the Brownian motion.

    abstract::Let T(k) (epsilon)(lambda; t(1),..., t(k)) = rho(X(t) (1))q(epsilon)(X(t) (2) - X(t) (1))... q(epsilon)(X(t(k) ) - X(t(k) )-1), where X(t) is a Brownian motion in R(2), lambda(dx) = rho(x)dx, and q(epsilon) converges to Dirac's delta function as epsilon downward arrow 0. The self-intersection local times of order k ar...

    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.83.11.3575

    authors: Dynkin EB

    更新日期:1986-06-01 00:00:00

  • Survey of large protein complexes in D. vulgaris reveals great structural diversity.

    abstract::An unbiased survey has been made of the stable, most abundant multi-protein complexes in Desulfovibrio vulgaris Hildenborough (DvH) that are larger than Mr approximately 400 k. The quaternary structures for 8 of the 16 complexes purified during this work were determined by single-particle reconstruction of negatively ...

    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.0813068106

    authors: Han BG,Dong M,Liu H,Camp L,Geller J,Singer M,Hazen TC,Choi M,Witkowska HE,Ball DA,Typke D,Downing KH,Shatsky M,Brenner SE,Chandonia JM,Biggin MD,Glaeser RM

    更新日期:2009-09-29 00:00:00

  • Impairment of antigen-specific antibody production in transgenic mice expressing a dominant-negative form of gp130.

    abstract::gp130 is a common signal-transducing receptor component for the interleukin 6 family of cytokines functioning in, for example, immune, hematopoietic, and nervous systems. In this study, to investigate the physiological functions of gp130 and to determine the pathological consequences of impaired gp130 signals, we have...

    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.94.6.2478

    authors: Kumanogoh A,Marukawa S,Kumanogoh T,Hirota H,Yoshida K,Lee IS,Yasui T,Yoshida K,Taga T,Kishimoto T

    更新日期:1997-03-18 00:00:00

  • Transcriptional repression of euchromatic genes by Drosophila heterochromatin protein 1 and histone modifiers.

    abstract::In Drosophila, heterochromatin protein 1 (HP1) suppresses the expression of euchromatic genes that are artificially translocated adjacent to heterochromatin by expanding heterochromatin structure into neighboring euchromatin. The purpose of this study was to determine whether HP1 functions as a transcriptional repress...

    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.211303598

    authors: Hwang KK,Eissenberg JC,Worman HJ

    更新日期:2001-09-25 00:00:00

  • Histone deacetylase inhibitor treatment dramatically reduces cholesterol accumulation in Niemann-Pick type C1 mutant human fibroblasts.

    abstract::Niemann-Pick type C (NPC) disease is predominantly caused by mutations in the NPC1 protein that affect intracellular cholesterol trafficking and cause accumulation of unesterified cholesterol and other lipids in lysosomal storage organelles. We report the use of a series of small molecule histone deacetylase (HDAC) in...

    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.1014890108

    authors: Pipalia NH,Cosner CC,Huang A,Chatterjee A,Bourbon P,Farley N,Helquist P,Wiest O,Maxfield FR

    更新日期:2011-04-05 00:00:00

  • Holomorphic curves in surfaces of general type.

    abstract::This note answers some questions on holomorphic curves and their distribution in an algebraic surface of positive index. More specifically, we exploit the existence of natural negatively curved "pseudo-Finsler" metrics on a surface S of general type whose Chern numbers satisfy c(2)1>2c2 to show that a holomorphic map ...

    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.87.1.80

    authors: Lu SS,Yau ST

    更新日期:1990-01-01 00:00:00

  • Pronounced zonal heterogeneity in Eocene southern high-latitude sea surface temperatures.

    abstract::Paleoclimate studies suggest that increased global warmth during the Eocene epoch was greatly amplified at high latitudes, a state that climate models cannot fully reproduce. However, proxy estimates of Eocene near-Antarctic sea surface temperatures (SSTs) have produced widely divergent results at similar latitudes, 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.1321441111

    authors: Douglas PM,Affek HP,Ivany LC,Houben AJ,Sijp WP,Sluijs A,Schouten S,Pagani M

    更新日期:2014-05-06 00:00:00

  • An algebraic description of stereochemical correspondence.

    abstract::It is shown that a stereochemical correspondence between two molecular systems can be represented by a commuting diagram of the point groups and permutation groups involved. The effect of the diagrammatic condition on the mappings of the cosets, double cosets, subgroup lattice, and double coset algebra determined for ...

    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.72.6.2385

    authors: Nourse JG

    更新日期:1975-06-01 00:00:00

  • Algorithmic design of self-assembling structures.

    abstract::We study inverse statistical mechanics: how can one design a potential function so as to produce a specified ground state? In this article, we show that unexpectedly simple potential functions suffice for certain symmetrical configurations, and we apply techniques from coding and information theory to provide mathemat...

    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.0901636106

    authors: Cohn H,Kumar A

    更新日期:2009-06-16 00:00:00

  • An integral membrane component of coatomer-coated transport vesicles defines a family of proteins involved in budding.

    abstract::We have isolated a major integral membrane protein from Golgi-derived coatomer-coated vesicles. This 24-kDa protein, p24, defines a family of integral membrane proteins with homologs present in yeast and humans. In addition to sequence similarity, all p24 family members contain a motif with the characteristic heptad r...

    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.92.17.8011

    authors: Stamnes MA,Craighead MW,Hoe MH,Lampen N,Geromanos S,Tempst P,Rothman JE

    更新日期:1995-08-15 00:00:00

  • Killing niche competitors by remote-control bacteriophage induction.

    abstract::A surprising example of interspecies competition is the production by certain bacteria of hydrogen peroxide at concentrations that are lethal for others. A case in point is the displacement of Staphylococcus aureus by Streptococcus pneumoniae in the nasopharynx, which is of considerable clinical significance. How it 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.0809600106

    authors: Selva L,Viana D,Regev-Yochay G,Trzcinski K,Corpa JM,Lasa I,Novick RP,Penadés JR

    更新日期:2009-01-27 00:00:00

  • Identification of functional domains of human erythrocyte spectrin.

    abstract::Isolated human erythrocyte spectrin is a dimer of two unique polypeptide chains. The dimer (alpha beta) undergoes reversible salt- and temperature-dependent association to form (alpha beta)2 tetramers. Spectrin also binds with high affinity to a protein receptor on the cytoplasmic surface of erythrocyte membrane vesic...

    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.77.11.6592

    authors: Morrow JS,Speicher DW,Knowles WJ,Hsu CJ,Marchesi VT

    更新日期:1980-11-01 00:00:00

  • Molecular underpinnings of cytoskeletal cross-talk.

    abstract::Cross-talk between the microtubule and actin networks has come under intense scrutiny following the realization that it is crucial for numerous essential processes, ranging from cytokinesis to cell migration. It is becoming increasingly clear that proteins long-considered highly specific for one or the other cytoskele...

    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.1917964117

    authors: Oberhofer A,Reithmann E,Spieler P,Stepp WL,Zimmermann D,Schmid B,Frey E,Ökten Z

    更新日期:2020-02-25 00:00:00

  • Lipocalin-type prostaglandin D synthase/beta-trace is a major amyloid beta-chaperone in human cerebrospinal fluid.

    abstract::The conformational change in amyloid beta (Abeta) peptide from its monomeric form to aggregates is crucial in the pathogenesis of Alzheimer's disease (AD). In the healthy brain, some unidentified chaperones appear to prevent the aggregation of Abeta. Here we reported that lipocalin-type prostaglandin D synthase (L-PGD...

    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.0701585104

    authors: Kanekiyo T,Ban T,Aritake K,Huang ZL,Qu WM,Okazaki I,Mohri I,Murayama S,Ozono K,Taniike M,Goto Y,Urade Y

    更新日期:2007-04-10 00:00:00

  • Measuring single-cell density.

    abstract::We have used a microfluidic mass sensor to measure the density of single living cells. By weighing each cell in two fluids of different densities, our technique measures the single-cell mass, volume, and density of approximately 500 cells per hour with a density precision of 0.001 g mL(-1). We observe that the intrins...

    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.1104651108

    authors: Grover WH,Bryan AK,Diez-Silva M,Suresh S,Higgins JM,Manalis SR

    更新日期:2011-07-05 00:00:00

  • Mimicking the folding pathway to improve homology-free protein structure prediction.

    abstract::Since the demonstration that the sequence of a protein encodes its structure, the prediction of structure from sequence remains an outstanding problem that impacts numerous scientific disciplines, including many genome projects. By iteratively fixing secondary structure assignments of residues during Monte Carlo simul...

    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.0811363106

    authors: DeBartolo J,Colubri A,Jha AK,Fitzgerald JE,Freed KF,Sosnick TR

    更新日期:2009-03-10 00:00:00

  • Asymmetric cryo-EM structure of the canonical Allolevivirus Qβ reveals a single maturation protein and the genomic ssRNA in situ.

    abstract::Single-stranded (ss) RNA viruses infect all domains of life. To date, for most ssRNA virions, only the structures of the capsids and their associated protein components have been resolved to high resolution. Qβ, an ssRNA phage specific for the conjugative F-pilus, has a T = 3 icosahedral lattice of coat proteins assem...

    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.1609482113

    authors: Gorzelnik KV,Cui Z,Reed CA,Jakana J,Young R,Zhang J

    更新日期:2016-10-11 00:00:00

  • Vasopressin modulates the spontaneous electrical activity in aortic cells (line A7r5) by acting on three different types of ionic channels.

    abstract::A7r5 smooth muscle (aorta) cells have a spontaneous electrical activity. Application of vasopressin produces a hyperpolarization accompanied by an interruption of the spontaneous activity, which is followed by a depolarization associated with a recovery of the spiking activity. Vasopressin action is produced by an act...

    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.85.23.9365

    authors: Van Renterghem C,Romey G,Lazdunski M

    更新日期:1988-12-01 00:00:00

  • Simple model for tuberculosis in cattle and badgers.

    abstract::As an aid to the study of bovine tuberculosis (TB), a simple model has been developed of an epidemic involving two species, cattle and badgers. Each species may infect the other. The proportion of animals affected is assumed relatively small so that the usual nonlinear aspects of epidemic theory are avoided. The model...

    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.0509003102

    authors: Cox DR,Donnelly CA,Bourne FJ,Gettinby G,McInerney JP,Morrison WI,Woodroffe R

    更新日期:2005-12-06 00:00:00

  • Nanoscale spatial organization of the HoxD gene cluster in distinct transcriptional states.

    abstract::Chromatin condensation plays an important role in the regulation of gene expression. Recently, it was shown that the transcriptional activation of Hoxd genes during vertebrate digit development involves modifications in 3D interactions within and around the HoxD gene cluster. This reorganization follows a global trans...

    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.1517972112

    authors: Fabre PJ,Benke A,Joye E,Nguyen Huynh TH,Manley S,Duboule D

    更新日期:2015-11-10 00:00:00

  • How nature can exploit nonspecific catalytic and carbohydrate binding modules to create enzymatic specificity.

    abstract::Noncatalytic carbohydrate binding modules (CBMs) are components of glycoside hydrolases that attack generally inaccessible substrates. CBMs mediate a two- to fivefold elevation in the activity of endo-acting enzymes, likely through increasing the concentration of the appended enzymes in the vicinity of the substrate. ...

    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.1212034109

    authors: Cuskin F,Flint JE,Gloster TM,Morland C,Baslé A,Henrissat B,Coutinho PM,Strazzulli A,Solovyova AS,Davies GJ,Gilbert HJ

    更新日期:2012-12-18 00:00:00

  • The nucleotide-binding site of bacterial translation initiation factor 2 (IF2) as a metabolic sensor.

    abstract::Translational initiation factor 2 (IF2) is a guanine nucleotide-binding protein that can bind guanosine 3',5'-(bis) diphosphate (ppGpp), an alarmone involved in stringent response in bacteria. In cells growing under optimal conditions, the GTP concentration is very high, and that of ppGpp very low. However, under stre...

    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.0606384103

    authors: Milon P,Tischenko E,Tomsic J,Caserta E,Folkers G,La Teana A,Rodnina MV,Pon CL,Boelens R,Gualerzi CO

    更新日期:2006-09-19 00:00:00

  • Macropredatory ichthyosaur from the Middle Triassic and the origin of modern trophic networks.

    abstract::The biotic recovery from Earth's most severe extinction event at the Permian-Triassic boundary largely reestablished the preextinction structure of marine trophic networks, with marine reptiles assuming the predator roles. However, the highest trophic level of today's marine ecosystems, i.e., macropredatory tetrapods ...

    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.1216750110

    authors: Fröbisch NB,Fröbisch J,Sander PM,Schmitz L,Rieppel O

    更新日期:2013-01-22 00:00:00

  • Genetically engineering Synechocystis sp. Pasteur Culture Collection 6803 for the sustainable production of the plant secondary metabolite p-coumaric acid.

    abstract::p-Coumaric acid is the precursor of phenylpropanoids, which are plant secondary metabolites that are beneficial to human health. Tyrosine ammonia lyase catalyzes the production of p-coumaric acid from tyrosine. Because of their photosynthetic ability and biosynthetic versatility, cyanobacteria are promising candidates...

    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.1323725111

    authors: Xue Y,Zhang Y,Cheng D,Daddy S,He Q

    更新日期:2014-07-01 00:00:00

  • Redundant control of the Caenorhabditis elegans sperm/oocyte switch by PUF-8 and FBF-1, two distinct PUF RNA-binding proteins.

    abstract::PUF proteins control both growth and differentiation in the C. elegans germ line. These conserved RNA-binding proteins inhibit expression of target mRNAs, either by repressing translation or promoting degradation. Previous studies showed that PUF-8, a PUF protein with striking similarity to human Pumilio, prevents ret...

    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.0504593102

    authors: Bachorik JL,Kimble J

    更新日期:2005-08-02 00:00:00

  • World food trends and prospects to 2025.

    abstract::This paper reviews food (especially cereal) production trends and prospects for the world and its main regions. Despite fears to the contrary, in recent years we have seen continued progress toward better methods of feeding humanity. Sub-Saharan Africa is the sole major exception. Looking to the future, this paper arg...

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

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.96.11.5929

    authors: Dyson T

    更新日期:1999-05-25 00:00:00

  • Inhibition of homologous recombination by variants of the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs).

    abstract::Two major DNA double-strand break repair pathways exist in all eukaryotes, nonhomologous DNA end joining (NHEJ) and homologous recombination (HR). Although both pathways can function throughout the cell cycle, NHEJ predominates in G0/G1) (when a replicated sister chromatid is unavailable), whereas HR makes a more subs...

    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.0406466102

    authors: Convery E,Shin EK,Ding Q,Wang W,Douglas P,Davis LS,Nickoloff JA,Lees-Miller SP,Meek K

    更新日期:2005-02-01 00:00:00

  • Hypophagia and metabolic adaptations in mice with defective ATGL-mediated lipolysis cause resistance to HFD-induced obesity.

    abstract::Adipose triglyceride lipase (ATGL) initiates intracellular triglyceride (TG) catabolism. In humans, ATGL deficiency causes neutral lipid storage disease with myopathy (NLSDM) characterized by a systemic TG accumulation. Mice with a genetic deletion of ATGL (AKO) also accumulate TG in many tissues. However, neither NLS...

    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.1516004112

    authors: Schreiber R,Hofer P,Taschler U,Voshol PJ,Rechberger GN,Kotzbeck P,Jaeger D,Preiss-Landl K,Lord CC,Brown JM,Haemmerle G,Zimmermann R,Vidal-Puig A,Zechner R

    更新日期:2015-11-10 00:00:00

  • Most central nervous system D2 dopamine receptors are coupled to their effectors by Go.

    abstract::We reported previously that Go-deficient mice develop severe neurological defects that include hyperalgesia, a generalized tremor, lack of coordination, and a turning syndrome somewhat reminiscent of unilateral lesions of the dopaminergic nigro-striatal pathway. By using frozen coronal sections of serially sectioned 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.051632598

    authors: Jiang M,Spicher K,Boulay G,Wang Y,Birnbaumer L

    更新日期:2001-03-13 00:00:00