Abstract:
:Membrane-integrated type II phosphatidic acid phosphatases (PAP2s) are important for numerous bacterial to human biological processes, including glucose transport, lipid metabolism, and signaling. Escherichia coli phosphatidylglycerol-phosphate phosphatase B (ecPgpB) catalyzes removing the terminal phosphate group from a lipid carrier, undecaprenyl pyrophosphate, and is essential for transport of many hydrophilic small molecules across the membrane. We determined the crystal structure of ecPgpB at a resolution of 3.2 Å. This structure shares a similar folding topology and a nearly identical active site with soluble PAP2 enzymes. However, the substrate binding mechanism appears to be fundamentally different from that in soluble PAP2 enzymes. In ecPgpB, the potential substrate entrance to the active site is located in a cleft formed by a V-shaped transmembrane helix pair, allowing lateral movement of the lipid substrate entering the active site from the membrane lipid bilayer. Activity assays of point mutations confirmed the importance of the catalytic residues and potential residues involved in phosphate binding. The structure also suggests an induced-fit mechanism for the substrate binding. The 3D structure of ecPgpB serves as a prototype to study eukaryotic PAP2 enzymes, including human glucose-6-phosphatase, a key enzyme in the homeostatic regulation of blood glucose concentrations.
journal_name
Proc Natl Acad Sci U S Aauthors
Fan J,Jiang D,Zhao Y,Liu J,Zhang XCdoi
10.1073/pnas.1403097111subject
Has Abstractpub_date
2014-05-27 00:00:00pages
7636-40issue
21eissn
0027-8424issn
1091-6490pii
1403097111journal_volume
111pub_type
杂志文章abstract::In extracts of interferon-treated HeLa cells, RNA covalently linked to double-stranded RNA (dsRNA) is preferentially degraded compared with mRNA not linked in dsRNA. This was established by following the degradation of poly(A)-containing mRNA annealed with poly(U), of poly(C)-containing encephalomyocarditis virus RNA ...
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.76.6.2600
更新日期:1979-06-01 00:00:00
abstract::An elegant expression is obtained for the product of the inverse Weierstrass-Laguerre transforms of two functions in terms of their convolution. It is also shown how the main result can be extended to hold for the product of the inverse Weierstrass-Laguerre transforms of several functions. ...
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.68.3.554
更新日期:1971-03-01 00:00:00
abstract::We present a comparative study of calorimetrically derived thermodynamic profiles for the binding of a series of drugs with selected DNA host duplexes. We use these data to demonstrate that comparisons between complete thermodynamic profiles (delta G zero, delta H zero, delta S zero, delta Cp) are required before drug...
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.84.24.8922
更新日期:1987-12-01 00:00:00
abstract::Molecular imaging probes have potential for in vivo identification of apoptosis and other intracellular processes. TcapQ, a cell-penetrating, near-infrared fluorescent peptide probe designed to be optically silent through intramolecular fluorescence quenching and activated by effector caspases, has been previously des...
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.0812884106
更新日期:2009-06-09 00:00:00
abstract::An ATP-hydrolyzing activity with the properties of a Mg(2+)-dependent (Na(+),K(+))-ATPase (ATP phosphohydrolase, EC 3.6.1.3) from a 20-fold purified plasma membrane fraction of the marine diatom, Nitzschia alba is described. The basal activity requires Mg(2+) and further stimulation by Na(+) or Na(+) plus K(+) is depe...
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.71.11.4376
更新日期:1974-11-01 00:00:00
abstract::Ovulation induces cyclic rupture and regenerative repair of the ovarian coelomic epithelium. This process of repeated disruption and repair accompanied by complex remodeling typifies a somatic stem/progenitor cell-mediated process. Using BrdU incorporation and doxycycline inducible histone2B-green fluorescent protein ...
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.0805012105
更新日期:2008-08-26 00:00:00
abstract::The retinoblastoma gene product (the RB protein) is phosphorylated in a cell cycle-dependent manner and this modification is believed to be important for cells to progress through the cell cycle. We found that purified cdk2 (cyclin-dependent kinase/cell division kinase 2) can phosphorylate the RB protein in vitro at 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.89.17.7900
更新日期:1992-09-01 00:00:00
abstract::Recent findings demonstrated proinflammatory functions of interleukin (IL)-9-producing T helper type (Th) 9 cells in the pathogenesis of intestinal bowel diseases (IBDs). However, also antiinflammatory properties have been ascribed to Th9 cells, pointing to a functional heterogeneity. To dissect the specific expressio...
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.1708329115
更新日期:2018-03-27 00:00:00
abstract::Originally identified as an essential component of the herpes simplex virus immediate early (IE) gene enhancer complex, the transcriptional coactivator host cell factor-1 (HCF-1) has been implicated in a broad range of cellular regulatory circuits. The protein mediates activation through multiple interactions with tra...
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.0704351104
更新日期:2007-06-26 00:00:00
abstract::Pbx-regulating protein-1 (Prep1) is a tumor suppressor, whereas myeloid ecotropic viral integration site-1 (Meis1) is an oncogene. We show that, to perform these activities in mouse embryonic fibroblasts, both proteins competitively heterodimerize with pre-B-cell leukemia homeobox-1 (Pbx1). Meis1 alone transforms Prep...
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.1321200111
更新日期:2014-03-11 00:00:00
abstract::Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid (AA) and its ester analog, 2-arachidonoylglycerol (2-AG), to prostaglandins (PGs) and prostaglandin glyceryl esters (PG-Gs), respectively. Although the efficiency of oxygenation of these substrates by COX-2 in vitro is similar, cellular biosynthesis of PGs far excee...
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.1507307112
更新日期:2015-10-06 00:00:00
abstract::The microsomal triglyceride (TG) transfer protein (MTP) is a heterodimeric lipid transfer protein that catalyzes the transport of triglyceride, cholesteryl ester, and phosphatidylcholine between membranes. Previous studies showing that the proximal cause of abetalipoproteinemia is an absence of MTP indicate that MTP 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.93.21.11991
更新日期:1996-10-15 00:00:00
abstract::Knowledge of how insects are actually affected by sex pheromones deployed throughout a crop so as to disrupt mating has lacked a mechanistic framework sufficient for guiding optimization of this environmentally friendly pest-control tactic. Major hypotheses are competitive attraction, desensitization, and camouflage. ...
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.0908453107
更新日期:2010-01-05 00:00:00
abstract::Prions are thought to consist mainly or entirely of misfolded PrP, a constitutively expressed host protein. Prions associated with the same PrP sequence may occur in the form of different strains; the strain phenotype is believed to be encoded by the conformation of the PrP. Some cell lines can be persistently infecte...
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.0710054104
更新日期:2007-12-26 00:00:00
abstract::One of the most long-lived models in plant science is the belief that the long-distance transport and ratio of two plant hormones, auxin and cytokinin, at the site of action control major developmental events such as apical dominance. We have used in vivo deuterium labeling and mass spectrometry to investigate the dyn...
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.0402504101
更新日期:2004-05-25 00:00:00
abstract::Protein prenylation with farnesyl or geranylgeranyl moieties is an important posttranslational modification that affects the activity of such diverse proteins as the nuclear lamins, the yeast mating factor mata, and the ras oncogene products. In this article, we show that whole retinal cultures incorporate radioactive...
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.87.19.7673
更新日期:1990-10-01 00:00:00
abstract::With the use of dynamic Monte Carlo simulations, the necessary conditions for the collapse from a random-coil denatured state to a structurally unique four-member beta-barrel native state of a model globular protein have been investigated. These systems are free to roam through all of configuration space--both native ...
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.85.14.5057
更新日期:1988-07-01 00:00:00
abstract::Nicotiana tabacum cv. Turkish Samsun NN plants were transformed with a modified and truncated replicase gene encoded by RNA-2 of cucumber mosaic virus strain Fny. The replicase gene had been modified by deleting a 94-base-pair region spanning nucleotides 1857-1950; the deletion also caused a shift in the open reading ...
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.89.18.8759
更新日期:1992-09-15 00:00:00
abstract::The phosphatase and tensin homolog (PTEN) is a tumor suppressor that is inactivated in many human cancers. PTEN loss has been associated with resistance to inhibitors of the epidermal growth factor receptor (EGFR), but the molecular basis of this resistance is unclear. It is believed that unopposed phosphatidylinosito...
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.0911188107
更新日期:2010-04-06 00:00:00
abstract::Six overlapping cosmid clones having an average insert size of 40 kilobase pairs were identified and isolated from a human genomic library by using a cDNA probe, Alu-7, specific for the amino acid sequence of C4d, a known region of the fourth component of human complement. Analysis of these genomic clones by restricti...
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.80.1.264
更新日期:1983-01-01 00:00:00
abstract::Production of reactive oxygen intermediates (ROI) and a form of programmed cell death called hypersensitive response (HR) are often associated with disease resistance of plants. We have previously shown that the Rac homolog of rice, OsRac1, is a regulator of ROI production and cell death in rice. Here we show that 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.021273498
更新日期:2001-01-16 00:00:00
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
更新日期:2000-02-29 00:00:00
abstract::By using differential display PCR, we have identified 98 cDNA fragments from the rat dorsal hippocampus that are expressed differentially between the fast learners and slow learners in the water maze learning task. One of these cDNA fragments encodes the rat serum- and glucocorticoid-inducible kinase (sgk) gene. North...
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.062405399
更新日期:2002-03-19 00:00:00
abstract::Plant morphogenesis requires coordinated cytoplasmic growth, oriented cell wall extension, and cell cycle progression, but it is debated which of these processes are primary drivers for tissue growth and directly targeted by developmental genes. Here, we used ChIP high-throughput sequencing combined with transcriptome...
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.1320457111
更新日期:2014-02-18 00:00:00
abstract::We utilized the presence of hepatic receptors for galactose-terminal glycoproteins to achieve specific rescue of differentiated hepatocytes from methotrexate toxicity. This was accomplished by administration of a conjugate formed by covalent coupling of the methotrexate antagonist, folinic acid (leucovorin), to galact...
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.80.10.3078
更新日期:1983-05-01 00:00:00
abstract::Amplitude-modulated phosphorescence/microwave double-resonance (AM-PMDR) spectra are reported for complexes of methylmercury(II) cation, designated CH3Hg(II), with tryptophan and glyceraldehyde-3-phosphate dehydrogenase (GPDHase; from rabbit muscle). Wavelength shifts are observed in the AM-PMDR spectra of CH3Hg(II)-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.79.14.4313
更新日期:1982-07-01 00:00:00
abstract::Bovine adrenal medullary cells, cultured on quartz plates, were superfused with buffer to which pulses of stimulant were added. Cytosolic Ca2+ was measured by the fura-2 fluorescence method and the simultaneously released catecholamine was measured electrochemically. When stimulant concentrations were adjusted to give...
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.86.24.9881
更新日期:1989-12-01 00:00:00
abstract::The pharmacokinetic analysis of dynamic-contrast-enhanced (DCE) MRI data yields K(trans) and k(ep), two parameters independently measuring the capillary wall contrast reagent transfer rate. The almost universally used standard model (SM) embeds the implicit assumption that equilibrium transcytolemmal water exchange is...
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.0711226105
更新日期:2008-11-18 00:00:00
abstract::Gene expression in higher organisms is thought to be regulated by a complex network of transcription factor binding and chromatin modifications, yet the relative importance of these two factors remains a matter of debate. Here, we show that a computational approach allows surprisingly accurate prediction of histone 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.1412081111
更新日期:2014-09-16 00:00:00
abstract::Cancers frequently arise as a result of an acquired genomic instability and the subsequent clonal evolution of neoplastic cells with variable patterns of genetic aberrations. Thus, the presence and behaviors of distinct clonal populations in each patient's tumor may underlie multiple clinical phenotypes in cancers. We...
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.1104009108
更新日期:2011-07-19 00:00:00