Abstract:
:We report the results of crystallographic difference maps at 3.0-A resolution of complexes of metal-nucleoside triphosphates with aspartate carbamoyltransferase (carbamoylphosphate:L-aspartate carbamoyltransferase, EC 2.1.3.2) from Escherichia coli. The complexes Gd3+-ATP, Al3+-ATP, and Gd3+-CTP bind to the allosteric effector domain of the enzyme in nearly the same orientation as the metal-free nucleotides. The result is consistent with kinetic observations of nearly identical allosteric efficacy of ATP and CTP and their complexes with cations. The effector Gd3+-GTP, however, binds in a distinctly different conformation and location than does 8-bromoguanosine 5'-triphosphate, reported in a separate investigation [Honzatko, R. B. & Lipscomb, W.N. (1982) J. Mol. Biol. 160, 265-286]. The difference in the binding modes of Gd3+-GTP and the bromo derivative suggests a possible mechanism for the relief of allosteric inhibition of GTP due to metal cations. We observe no binding of metal-nucleoside triphosphates in the region of the phosphate crevice of aspartate carbamoyltransferase, consistent with the reduced ability of metal nucleotides to compete with carbamoyl phosphate for the active site. However, a single Gd3+ ion binds in the region of the active site as evidenced by strong density. The binding of cations near the active site probably causes the inhibition of catalysis observed in kinetics experiments reported earlier [Honzatko, R.B., Lauritzen, A.M. & Lipscomb, W.N. (1981) Proc. Natl. Acad. Sci. USA 78, 898-902].
journal_name
Proc Natl Acad Sci U S Aauthors
Honzatko RB,Lipscomb WNdoi
10.1073/pnas.79.23.7171subject
Has Abstractpub_date
1982-12-01 00:00:00pages
7171-4issue
23eissn
0027-8424issn
1091-6490journal_volume
79pub_type
杂志文章abstract::Colorectal cancer is the second leading cause of cancer-related deaths in the United States. Understanding the distinct genetic and epigenetic changes contributing to the establishment and growth of metastatic lesions is crucial for the development of novel therapeutic strategies. In a search for key regulators of col...
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.0810715105
更新日期:2008-12-23 00:00:00
abstract::The allocation of carbon and nitrogen resources to the synthesis of plant proteins, carbohydrates, and lipids is complex and under the control of many genes; much remains to be understood about this process. QQS (Qua-Quine Starch; At3g30720), an orphan gene unique to Arabidopsis thaliana, regulates metabolic processes...
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.1514670112
更新日期:2015-11-24 00:00:00
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
更新日期:2004-04-27 00:00:00
abstract::Mitochondrial DNAs were prepared from maize lines with normal cytoplasm and with the T, C, S, and EP sources of male-sterile cytoplasms. Agarose gel electrophoresis of these preparations revealed a main high-molecular-weight DNA band. In addition, the S cytoplasm was characterized by the presence of two faster migrati...
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.74.7.2904
更新日期:1977-07-01 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 Eemian (last interglacial, 130-115 ka) was likely the warmest of all interglacials of the last 800 ka, with summer Arctic temperatures 3-5 °C above present. Here, we present improved Eemian climate records from central Greenland, reconstructed from the base of the Greenland Ice Sheet Project 2 (GISP2) ice core. Ou...
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.1524766113
更新日期:2016-08-30 00:00:00
abstract::Three naturally occurring dermorphin-like peptides from the skin of the frog Phyllomedusa bicolor, the related carboxyl-terminal amides, and some substituted analogs were synthesized, their binding profiles to opioid receptors were determined, and their biological activities were studied in isolated organ preparations...
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.89.15.7203
更新日期:1992-08-01 00:00:00
abstract::Future nuclear arms reduction efforts will require technologies to verify that warheads slated for dismantlement are authentic without revealing any sensitive weapons design information to international inspectors. Despite several decades of research, no technology has met these requirements simultaneously. Recent wor...
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.1721278115
更新日期:2018-04-24 00:00:00
abstract::Mach bands, the illusory brightness maxima and minima perceived at the initiation and termination of luminance gradients, respectively, are generally considered a direct perceptual manifestation of lateral inhibitory interactions among retinal or other lower order visual neurons. Here we examine an alternative explana...
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.96.9.5239
更新日期:1999-04-27 00:00:00
abstract::Enhancing immune responses with immune-modulatory monoclonal antibodies directed to inhibitory immune receptors is a promising modality in cancer therapy. Clinical efficacy has been demonstrated with antibodies blocking inhibitory immune checkpoints such as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) or PD-1/...
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.1417320112
更新日期:2015-05-12 00:00:00
abstract::Infectious tolerance describes the process of CD4(+) regulatory T cells (Tregs) converting naïve T cells to become additional Tregs. We show that antigen-specific Tregs induce, within skin grafts and dendritic cells, the expression of enzymes that consume at least 5 different essential amino acids (EAAs). T cells fail...
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.0903919106
更新日期:2009-07-21 00:00:00
abstract::Xenopus oocytes express a gene encoding bovine rhodopsin as well as its SP6 RNA polymerase-derived transcripts and total retinal mRNA. The opsin produced is in unglycosylated (30 kDa) and two glycosylated (35 kDa and 41 kDa) forms. Incubation of the cells expressing the above proteins with 11-cis-retinal generates rho...
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.85.21.7917
更新日期:1988-11-01 00:00:00
abstract::The circular dichroism data on 17 adenine nucleosides show that the 260- and 207-mmu absorption systems of the adenine chromophore each contain at least two electronic transitions. The CD maxima are commonly found at around 260, 220, and 200 mmu, and occasionally at 240 mmu. Solvent studies suggest that these CD bands...
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.62.1.22
更新日期:1969-01-01 00:00:00
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
更新日期:1993-09-15 00:00:00
abstract::Pharmacological treatments designed to reactivate fetal γ-globin can lead to an effective and successful clinical outcome in patients with hemoglobinopathies. However, new approaches remain highly desired because such treatments are not equally effective for all patients, and toxicity issues remain. We have taken a sy...
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.0912896107
更新日期:2010-09-28 00:00:00
abstract::In the mouse, axons of olfactory sensory neurons (OSNs) that express the same odorant receptor (OR) gene coalesce into one or a few glomeruli in the olfactory bulb. The positions of OR-specific glomeruli are traditionally described as stereotyped. Here, we have assessed quantitatively the positions of OR-specific glom...
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.1512135112
更新日期:2015-10-27 00:00:00
abstract::Preclinical animal models have largely ignored the immune-suppressive mechanisms that are important in human cancers. The identification and use of such models should allow better predictions of successful human responses to immunotherapy. As a model for changes induced in nonmalignant cells by cancer, we examined T-c...
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.0901166106
更新日期:2009-04-14 00:00:00
abstract::Break-induced replication (BIR) refers to recombination-dependent DNA synthesis initiated from one end of a DNA double-strand break and can extend for more than 100 kb. BIR initiates by Rad51-catalyzed strand invasion, but the mechanism for DNA synthesis is not known. Here, we used BrdU incorporation to track DNA synt...
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.1309800110
更新日期:2013-08-13 00:00:00
abstract::Are animals conscious? If so, when did consciousness evolve? We address these long-standing and essential questions using a modern neuroscientific approach that draws on diverse fields such as consciousness studies, evolutionary neurobiology, animal psychology, and anesthesiology. We propose that the stepwise emergenc...
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.1301188110
更新日期:2013-06-18 00:00:00
abstract::We describe an active polymer network in which processive molecular motors control network elasticity. This system consists of actin filaments cross-linked by filamin A (FLNa) and contracted by bipolar filaments of muscle myosin II. The myosin motors stiffen the network by more than two orders of magnitude by pulling ...
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.0903974106
更新日期:2009-09-08 00:00:00
abstract::Retrograde axonal transport plays an important role in the maintenance of neuronal functions, but the mechanism is poorly defined partly because the constituents of the retrograde transport system and their interactions have yet to be elucidated. Of special interest is how dynein/dynactin motor proteins interact with ...
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.0602222104
更新日期:2007-02-13 00:00:00
abstract::Nitroxyl anion (HNONO(-)), the one-electron reduced form of nitric oxide (NO), induces positive cardiac inotropy and selective venodilation in the normal in vivo circulation. Here we tested whether HNO/NO(-) augments systolic and diastolic function of failing hearts, and whether contrary to NO/nitrates such modulation...
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.0937302100
更新日期:2003-04-29 00:00:00
abstract::Two brefeldin A (BFA)-inhibited guanine nucleotide-exchange proteins for ADP-ribosylation factors, 200-kDa BIG1 and 190-kDa BIG2, were copurified from bovine brain cytosol associated with >670-kDa macromolecular complexes. When observed by immunofluorescence in HeLa S3 and HepG2 cells, endogenous BIG1 and coexpressed ...
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.97.6.2567
更新日期:2000-03-14 00:00:00
abstract::Reward-guided decision-making depends on a network of brain regions. Among these are the orbitofrontal and the anterior cingulate cortex. However, it is difficult to ascertain if these areas constitute anatomical and functional unities, and how these areas correspond between monkeys and humans. To address these questi...
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.1410767112
更新日期:2015-05-19 00:00:00
abstract::Maintenance of genomic stability is essential for normal organismal development and is vital to prevent diseases such as cancer. As genetic information is packaged into chromatin, it has become increasingly clear that the chromatin environment plays an important role in DNA damage response. However, how DNA repair 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.1324036111
更新日期:2014-05-13 00:00:00
abstract::The heart has not been regarded as a major target organ of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity notwithstanding that lethal cardiac dysfunction can occur in the absence of histopathological changes. To assess possible TCDD cardiotoxicity, we studied the effect of TCDD five days after treatment (10 micro...
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.85.3.905
更新日期:1988-02-01 00:00:00
abstract::Here we describe two mammalian transcription factors selectively expressed in the central nervous system. Both proteins, neuronal PAS domain protein (NPAS) 1 and NPAS2, are members of the basic helix-loop-helix-PAS family of transcription factors. cDNAs encoding mouse and human forms of NPAS1 and NPAS2 have been isola...
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.94.2.713
更新日期:1997-01-21 00:00:00
abstract::Proteolipid protein (PLP) is the major myelin membrane protein of the central nervous system. We have isolated a copy of an alternatively spliced PLP gene transcript from a mouse brain cDNA library that was screened for PLP-related sequences. The encoded 241-amino acid protein differs from PLP by an internal deletion ...
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.84.16.5665
更新日期:1987-08-01 00:00:00
abstract::The hydroxyproline-containing proteins (hyproproteins) synthesized by cultured human fibroblasts have been partially characterized. The hyproprotein extracted from the cell layer was found to be similar to the collagen extracted from skin in the ratio of hydroxyproline to proline, chain composition, solubility, and re...
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.68.2.454
更新日期:1971-02-01 00:00:00
abstract::Escherichia coli DnaJ functions as a typical molecular chaperone in coordination with other heat shock proteins such as DnaK and GrpE in a variety of cellular processes. In this study, it was found that E. coli possesses an analogue of DnaJ, as judged from not only its primary structure but also its possible function....
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.91.3.1054
更新日期:1994-02-01 00:00:00