Abstract:
:ATP-dependent RNA ligases are agents of RNA repair that join 3'-OH and 5'-PO4 RNA ends. Naegleria gruberi RNA ligase (NgrRnl) exemplifies a family of RNA nick-sealing enzymes found in bacteria, viruses, and eukarya. Crystal structures of NgrRnl at three discrete steps along the reaction pathway-covalent ligase-(lysyl-Nζ)-AMP•Mn(2+) intermediate; ligase•ATP•(Mn(2+))2 Michaelis complex; and ligase•Mn(2+) complex-highlight a two-metal mechanism of nucleotidyl transfer, whereby (i) an enzyme-bound "catalytic" metal coordination complex lowers the pKa of the lysine nucleophile and stabilizes the transition state of the ATP α phosphate; and (ii) a second metal coordination complex bridges the β- and γ-phosphates. The NgrRnl N domain is a distinctively embellished oligonucleotide-binding (OB) fold that engages the γ-phosphate and associated metal complex and orients the pyrophosphate leaving group for in-line catalysis with stereochemical inversion at the AMP phosphate. The unique domain architecture of NgrRnl fortifies the theme that RNA ligases have evolved many times, and independently, by fusions of a shared nucleotidyltransferase domain to structurally diverse flanking modules. The mechanistic insights to lysine adenylylation gained from the NgrRnl structures are likely to apply broadly to the covalent nucleotidyltransferase superfamily of RNA ligases, DNA ligases, and RNA capping enzymes.
journal_name
Proc Natl Acad Sci U S Aauthors
Unciuleac MC,Goldgur Y,Shuman Sdoi
10.1073/pnas.1516536112subject
Has Abstractpub_date
2015-11-10 00:00:00pages
13868-73issue
45eissn
0027-8424issn
1091-6490pii
1516536112journal_volume
112pub_type
杂志文章abstract::The role of protein kinase C (PKC) as a mediator of glucose-induced insulin secretion has been a subject of controversy. Glucose-induced translocation of PKC has not been reported, and the relevant PKC isoenzymes in islets have not been identified. To address these issues, we developed specific antibodies to the alpha...
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.87.24.9893
更新日期:1990-12-01 00:00:00
abstract::By commandeering cellular translation initiation factors, or destroying those dispensable for viral mRNA translation, viruses often suppress host protein synthesis. In contrast, cellular protein synthesis proceeds in human cytomegalovirus (HCMV)-infected cells, forcing viral and cellular mRNAs to compete for limiting ...
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.1202829109
更新日期:2012-04-10 00:00:00
abstract::Transcription, splicing, and translation are potentially coordinately regulatable in a temporospatial-dependent manner, although supporting experimental evidence for this notion is scarce. Yeast two-hybrid screening of a mammary gland cDNA library with human p21-activated kinase 1 (Pak1) as bait identified polyC-RNA-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.0701065104
更新日期:2007-04-03 00:00:00
abstract::Rat skeletal muscle selenoprotein W cDNA was isolated and sequenced. The isolation strategy involved design of degenerate PCR primers from reverse translation of a partial peptide sequence. A reverse transcription-coupled PCR product from rat muscle mRNA was used to screen a muscle cDNA library prepared from selenium-...
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.92.19.8749
更新日期:1995-09-12 00:00:00
abstract::Variation of chloroplast DNA and nuclear ribosomal DNA (DNA encoding ribosomal RNA) was studied for five species of white oak native to the eastern United States. Although these species differ in many morphological characters and have different (though overlapping) geographical ranges and ecological tolerances, they 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.88.6.2540
更新日期:1991-03-15 00:00:00
abstract::Specific binding properties of the tritium-labeled delta opiate receptor agonist [3H][2-D-penicillamine, 5-D-penicillamine]enkephalin [( 3H][D-Pen2, D-Pen5]enkephalin) were characterized in the rat brain and in a mouse neuroblastoma-rat glioma hybrid cell line (NG 108-15). Saturation isotherms of [3H][D-Pen2, D-Pen5]e...
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.82.8.2543
更新日期:1985-04-01 00:00:00
abstract::Expressions are developed for weak single pair emission probability and strong emission average number of pairs. The water transparency cutoff is closely realized, showing that the fundamental time scale is even shorter. ...
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.90.10.4505
更新日期:1993-05-15 00:00:00
abstract::Evidence for hydrogen bonding between 5'-ribonucleotides in water has been obtained from a 220-MHz proton magnetic resonance study of nitrogenous protons. The amino groups of GMP, AMP, and CMP exhibit proton resonance lines which are somewhat broadened by proton exchange with the solvent at 0 degrees ; their downfield...
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.69.8.2025
更新日期:1972-08-01 00:00:00
abstract::To study the mechanism of arrest of DNA synthesis at d(TC)n and d(GA)n sequences, single-stranded DNA molecules including d(TC)27 or d(TC)31 tracts or a d(GA)27 tract were used as templates for in vitro assays of complementary DNA synthesis performed by extension of a primer with the Klenow polymerase or the Taq polym...
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.88.2.507
更新日期:1991-01-15 00:00:00
abstract::Genome duplication followed by massive gene loss has permanently shaped the genomes of many higher eukaryotes, particularly angiosperms. It has long been believed that a primary advantage of genome duplication is the opportunity for the evolution of genes with new functions by modification of duplicated genes. If so, ...
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.0507782103
更新日期:2006-02-21 00:00:00
abstract::We have shown previously that guanine nucleotide-binding protein (G protein) beta gamma complexes purified from bovine brain membranes are methyl esterified on a C-terminal cysteine residue of the gamma polypeptide. In the present study, 3H-methylated G beta gamma complexes cleaved to their constituent amino acids by ...
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.87.15.5868
更新日期:1990-08-01 00:00:00
abstract::Because of increased numbers of recorded pertussis cases in the United States, this study sought to understand the role of nonmedical vaccine exemptions and waning immunity may have had on the resurgence of pertussis in the United States at the community level. We used geospatial scan statistics, SaTScan, version 9.4,...
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.1700240114
更新日期:2017-07-03 00:00:00
abstract::Adenosine has been identified in the anterior pituitary gland and is secreted from cultured folliculostellate (FS) cells. To determine whether adenosine controls the secretion of anterior pituitary hormones in vitro, adenosine was incubated with anterior pituitaries. It stimulated prolactin (PRL) release at the lowest...
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.95.13.7795
更新日期:1998-06-23 00:00:00
abstract::Long-term depression (LTD) at cerebellar parallel fiber (PF)-Purkinje cell synapses must be balanced by long-term potentiation (LTP) to prevent saturation and allow reversal of motor learning. The only previously analyzed form of cerebellar LTP is induced by 4-8 Hz PF stimulation and requires cAMP but not nitric oxide...
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.122206399
更新日期:2002-06-11 00:00:00
abstract::Mesencephalic dopamine neurons from the embryonic mouse brain were dissociated, aggregated in vitro in the presence of dissociated cells from appropriate or inappropriate target neuron areas, and visualized by the Falck-Hillarp histofluorescence technique after exposure to 1 microM exogenous dopamine. When aggregated ...
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.78.2.1264
更新日期:1981-02-01 00:00:00
abstract::A promising strategy for DNA sequencing exploits transposons to provide mobile sites for the binding of sequencing primers. For such a strategy to be maximally efficient, the location and orientation of the transposon must be readily determined and the insertion sites should be randomly distributed. We demonstrate 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.87.16.6213
更新日期:1990-08-01 00:00:00
abstract::Many cellular cargoes move bidirectionally along microtubules, driven by teams of plus- and minus-end-directed motor proteins. To probe the forces exerted on cargoes during intracellular transport, we examined latex beads phagocytosed into living mammalian macrophages. These latex bead compartments (LBCs) are encased ...
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.1215462109
更新日期:2012-11-06 00:00:00
abstract::Mutant alleles at the dilute unconventional myosin heavy chain locus cause diluted coat color, opisthotonic seizures, and death. The dilute coat color phenotype is caused by irregular clumping of pigment in the hair, but amounts of melanin are unchanged from wild-type controls. The melanocyte phenotype has been descri...
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.93.25.14554
更新日期:1996-12-10 00:00:00
abstract::We have isolated a set of regulatory mutants defective in transcription termination at the attenuator in the leader region of the Escherichia coli tryptophan (trp) operon. In vivo the mutants have 2- to 4-fold increased levels of expression of the trp operon above the level of the trpR parental strain. These levels 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.75.10.4833
更新日期:1978-10-01 00:00:00
abstract::Influenza hemagglutinin (HA) is the primary target of the humoral response during infection/vaccination. Current influenza vaccines typically fail to elicit/boost broadly neutralizing antibodies (bnAbs), thereby limiting their efficacy. Although several bnAbs bind to the conserved stem domain of HA, focusing the immun...
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.1402766111
更新日期:2014-06-24 00:00:00
abstract::Focal cerebral ischemia and traumatic brain injury induce an escalating amount of cell death because of harmful mediators diffusing from the original lesion site. Evidence suggests that healthy cells surrounding these lesions attempt to protect themselves by producing endocannabinoids (eCBs) and activating cannabinoid...
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.0510418103
更新日期:2006-04-18 00:00:00
abstract::Two mouse monoclonal anti-anti-idiotopic antibodies (anti-anti-Id, Ab3), AF14 and AF52, were prepared by immunizing BALB/c mice with rabbit polyclonal anti-idiotypic antibodies (anti-Id, Ab2) raised against antibody D1.3 (Ab1) specific for the antigen hen egg lysozyme. AF14 and AF52 react with an "internal image" mono...
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.94.16.8697
更新日期:1997-08-05 00:00:00
abstract::Reproductive success is widely used as a measure of fitness. However, offspring quantity may not reflect the genetic contribution to subsequent generations if there is nonrandom variation in offspring quality. Offspring quality is likely to be an important component of human fitness, and tradeoffs between offspring qu...
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.1310058111
更新日期:2014-01-21 00:00:00
abstract::A method is presented for starting from a very-low-energy high-dimensional conformation and obtaining a low-energy three-dimensional structure by gradual contraction of the dimensionality. The contraction in dimensionality is achieved by use of Cayley-Menger determinants, of which a simplified form is derived here. Pr...
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.83.9.2782
更新日期:1986-05-01 00:00:00
abstract::We measured the superconducting transition temperature of (6)Li between 16 and 26 GPa, and report the lightest system to exhibit superconductivity to date. The superconducting phase diagram of (6)Li is compared with that of (7)Li through simultaneous measurement in a diamond anvil cell (DAC). Below 21 GPa, Li exhibits...
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.1412638112
更新日期:2015-01-06 00:00:00
abstract::It is well established that pregnancy early in life reduces the risk of breast cancer in women and that this effect is universal. This phenomenon of parity protection against mammary cancer is also observed in rodents. Earlier studies have demonstrated that short-term administration of estradiol (E) in combination wit...
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.201393798
更新日期:2001-09-25 00:00:00
abstract::For many agronomically important plant genes, only their position on a genetic map is known. In the absence of an efficient transposon tagging system, such genes have to be isolated by map-based cloning. In bread wheat Triticum aestivum, the genome is hexaploid, has a size of 1.6 x 10(10) bp, and contains more than 80...
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.230361597
更新日期:2000-11-21 00:00:00
abstract::The application of boron neutron capture therapy to rheumatoid arthritis requires the selective delivery of the boron-10 isotope to the synovitic tissue. The use of liposomes as a boron delivery method has been explored through the measurement of the time course biodistribution of boron in rats with collagen-induced 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.95.5.2531
更新日期:1998-03-03 00:00:00
abstract::To improve the efficiency of liposome-mediated DNA transfer as a tool for gene therapy, we have developed a fusigenic liposome vector based on principles of viral cell fusion. The fusion proteins of hemagglutinating virus of Japan (HVJ; also Sendai virus) are complexed with liposomes that encapsulate oligodeoxynucleot...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 评论,杂志文章,评审
doi:10.1073/pnas.93.21.11421
更新日期:1996-10-15 00:00:00
abstract::p19ARF has been implicated as a key regulator of p53 stability and activation. While numerous stresses activate the p53 growth arrest pathway, those requiring p19ARF remain to be elucidated. We used p19ARF knockout mouse embryo fibroblasts to show that DNA damage and microtubule disruption require p19ARF to induce p53...
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.050560997
更新日期:2000-03-28 00:00:00