Abstract:
:The herpes simplex virus DNA polymerase consists of two subunits--a catalytic subunit and an accessory subunit, UL42, that increases processivity. Mutations affecting the extreme C terminus of the catalytic subunit specifically disrupt subunit interactions and ablate virus replication, suggesting that new antiviral drugs could be rationally designed to interfere with polymerase heterodimerization. To aid design, we performed circular dichroism (CD) spectroscopy and analytical ultracentrifugation studies, which revealed that a 36-residue peptide corresponding to the C terminus of the catalytic subunit folds into a monomeric structure with partial alpha-helical character. CD studies of shorter peptides were consistent with a model where two separate regions of alpha-helix interact to form a hairpin-like structure. The 36-residue peptide and a shorter peptide corresponding to the C-terminal 18 residues blocked UL42-dependent long-chain DNA synthesis at concentrations that had no effect on synthesis by the catalytic subunit alone or by calf thymus DNA polymerase delta and its processivity factor. These peptides, therefore, represent a class of specific inhibitors of herpes simplex virus DNA polymerase that act by blocking accessory-subunit-dependent synthesis. These peptides or their structures may form the basis for the synthesis of clinically effective drugs.
journal_name
Proc Natl Acad Sci U S Aauthors
Digard P,Williams KP,Hensley P,Brooks IS,Dahl CE,Coen DMdoi
10.1073/pnas.92.5.1456subject
Has Abstractpub_date
1995-02-28 00:00:00pages
1456-60issue
5eissn
0027-8424issn
1091-6490journal_volume
92pub_type
杂志文章abstract::The necroptosis cell death pathway has been implicated in host defense and in the pathology of inflammatory diseases. While phosphorylation of the necroptotic effector pseudokinase Mixed Lineage Kinase Domain-Like (MLKL) by the upstream protein kinase RIPK3 is a hallmark of pathway activation, the precise checkpoints ...
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.1919960117
更新日期:2020-04-14 00:00:00
abstract::The distribution of dopamine-containing processes in the striatum of fetal and neonatal cats was studied by immunohistochemical and glyoxylic acid histofluorescence methods and compared to the distribution of acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7) observed by thiocholine histochemistry in 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.78.9.5871
更新日期:1981-09-01 00:00:00
abstract::Many bacteria use acyl homoserine lactone signals to monitor cell density in a type of gene regulation termed quorum sensing and response. Synthesis of these signals is directed by homologs of the luxi gene of Vibrio fischeri. This communication resolves two critical issues concerning the synthesis of the V. fischeri ...
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.93.18.9505
更新日期:1996-09-03 00:00:00
abstract::Human T-cell leukemia virus type I (HTLV-I) is a causative agent of adult T-cell leukemia (ATL). To elucidate the role of HTLV-I in leukemogenesis, we examined the biological activity of a defective HTLV-I provirus with the env-pX 3' long terminal repeat region cloned from leukemic cells of an ATL patient. Transfectio...
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.87.3.1071
更新日期:1990-02-01 00:00:00
abstract::Heat shock protein 90-alpha (Hsp90alpha) is an intracellular molecular chaperone. However, it can also be secreted with the underlying regulatory mechanism remaining far from clear. Here we show that the secreted Hsp90alpha is a C-terminal truncated form and its secretion is regulated by the C-terminal EEVD motif via ...
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.0908151106
更新日期:2009-12-15 00:00:00
abstract::Diabetes mellitus is characterized by either the inability to produce insulin (type 1 diabetes) or as insensitivity to insulin secreted by the body (type 2 diabetes). In either case, the body is unable to move blood glucose efficiently across cell membranes to be used. This leads to a variety of local and systemic det...
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.1007884107
更新日期:2010-07-27 00:00:00
abstract::Motilin, [Met]enkephalin, [Leu]enkephalin, somatostatin, taurine, gamma-aminobutyric acid (GABA), and glycine were tested for their effects on Deiters neurons of the lateral vestibular nucleus in rabbits. Iontophoresis was carried out with multibarrelled micropipettes. All four peptides and three amino acids produced ...
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.79.10.3355
更新日期:1982-05-01 00:00:00
abstract::The acetylcholine receptor is a protein that contains certain critical disulfide bonds. Experiments were designed to determine the role such bonds might play in the physiological activity of the receptor. Modification of the receptor with sodium bisulfite and diamide produced an increase in the time constants of the m...
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.78.12.7806
更新日期:1981-12-01 00:00:00
abstract::Subtractive library construction and differential screening were used to identify a cDNA for a cell type-specific immediate early gene induced in rat PC12 pheochromocytoma cells. Sequencing identified the protein product of this gene as rat synaptotagmin IV (SytIV). Synaptotagmins are synaptic vesicle proteins thought...
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.92.6.2164
更新日期:1995-03-14 00:00:00
abstract::Gelation of colloidal nanocrystals emerged as a strategy to preserve inherent nanoscale properties in multiscale architectures. However, available gelation methods to directly form self-supported nanocrystal networks struggle to reliably control nanoscale optical phenomena such as photoluminescence and localized surfa...
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.1806927115
更新日期:2018-09-04 00:00:00
abstract::Previous studies in Saccharomyces cerevisiae have defined an essential role for the Dbf4-Cdc7 kinase complex in the initiation of DNA replication presumably by phosphorylation of target proteins, such as the minichromosome maintenance (Mcm) complex. We have examined the phosphorylation of the Mcm complex by the Dfp1-H...
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.0237384100
更新日期:2003-03-04 00:00:00
abstract::The autophagic ubiquitin-like protein (ublp) autophagy-related (ATG)12 is a component of the ATG12∼ATG5-ATG16L1 E3 complex that promotes lipid conjugation of members of the LC3 ublp family. A role of ATG12 in the E3 complex is to recruit the E2 enzyme ATG3. Here we report the identification of the ATG12 binding sequen...
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.1314755110
更新日期:2013-11-19 00:00:00
abstract::In earlier studies with the acetylcholine receptor (AcChoR) of Electrophorus electricus the rate and equilibrium constants for a model that relates the ligand binding to ion translocation were determined, and the dependence of these constants on the concentrations of carbamoylcholine and acetylcholine, over a 200- 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.79.4.963
更新日期:1982-02-01 00:00:00
abstract::Calcicludine (CaC) is a 60-amino acid polypeptide from the venom of Dendroaspis angusticeps. It is structurally homologous to the Kunitz-type protease inhibitor, to dendrotoxins, which block K+ channels, and to the protease inhibitor domain of the amyloid beta protein that accumulates in Alzheimer disease. Voltage-cla...
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.91.3.878
更新日期:1994-02-01 00:00:00
abstract::The antimicrobial peptide hepcidin appears to play a central role in the regulation of iron homeostasis. In intact animals, iron overload or the injection of lipopolysaccharide (LPS) stimulates transcription of HAMP, the gene that encodes hepcidin. In isolated hepatocytes, IL-6, an inflammatory cytokine the production...
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.0403108101
更新日期:2004-06-22 00:00:00
abstract::Disordered systems like liquids, gels, glasses, or granular materials are not only ubiquitous in daily life and in industrial applications, but they are also crucial for the mechanical stability of cells or the transport of chemical and biological agents in living organisms. Despite the importance of these systems, th...
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.2005638117
更新日期:2020-06-23 00:00:00
abstract::The amino-terminal sequences of two polypeptides with nonsuppressible insulin-like and cell-growth-promoting activities (NSILA I and II), isolated from human serum, were determined. Of the first 31 residues, 22 are identical in NSILA I and II. Moreover, a striking structural similarity was found between NSILA and insu...
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.73.12.4379
更新日期:1976-12-01 00:00:00
abstract::In an 1885 paper, E. Picard defined a subgroup Tau(Lambda) of PU(2,1) generated by monodromies and depending on parameters Lambda = (lambda(1),lambda(2),lambda(3),lambda(4)), 0 < lambda(i) < 1, < lambda(i) < 3, lambda(i) + lambda(j) >/= 1, 1 = i < j = 4. The family Tau(Lambda) resembles the family of groups Tau([u...
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.78.10.5948
更新日期:1981-10-01 00:00:00
abstract::Siphoviridae is the most abundant viral family on earth which infects bacteria as well as archaea. All known siphophages infecting gram+ Lactococcus lactis possess a baseplate at the tip of their tail involved in host recognition and attachment. Here, we report analysis of the p2 phage baseplate structure by X-ray cry...
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.1000232107
更新日期:2010-04-13 00:00:00
abstract::In this paper, Vafa's approach to the formulation of conformal field theories is combined with the formal calculus developed in Frenkel, Lepowsky, and Meurman's work on the vertex operator construction of the Monster to give a geometric definition of vertex operator algebras. The main result announced is the equivalen...
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.88.22.9964
更新日期:1991-11-15 00:00:00
abstract::The capacity of a so-called male recombination (MR) chromosome in Drosophila melanogaster to generate mutations at 14 X-chromosome loci specifying visible phenotypes was investigated. Appreciable increases in mutation were found at three loci y, sn, and ras. Tests of represnetative mutants generated at each locus esta...
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.74.8.3490
更新日期:1977-08-01 00:00:00
abstract::Kinesin-1 is a molecular motor protein that transports cargo along microtubules. Inside cells, the vast majority of kinesin-1 is regulated to conserve ATP and to ensure its proper intracellular distribution and coordination with other molecular motors. Regulated kinesin-1 folds in half at a hinge in its coiled-coil st...
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.0803575105
更新日期:2008-07-01 00:00:00
abstract::The callipyge mutation (CLPG) is an A to G transition that affects a muscle-specific long-range control element located in the middle of the 90-kb DLK1-GTL2 intergenic (IG) region. It causes ectopic expression of a 327-kb cluster of imprinted genes in skeletal muscle, resulting in the callipyge muscular hypertrophy 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.0602844103
更新日期:2006-05-23 00:00:00
abstract::MCF10A mammary epithelial cells form growth-arrested structures when cultured in three-dimensional basement membrane gels. Activation of the receptor tyrosine kinase ErbB2 induces formation of proliferative structures that share properties with noninvasive early stage lesions. We conducted a genetic screen to identify...
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.0308090100
更新日期:2004-02-03 00:00:00
abstract::Arabidopsis thaliana endosperm, a transient tissue that nourishes the embryo, exhibits extensive localized DNA demethylation on maternally inherited chromosomes. Demethylation mediates parent-of-origin-specific (imprinted) gene expression but is apparently unnecessary for the extensive accumulation of maternally biase...
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.1306164110
更新日期:2013-05-07 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::The constant heavy chain (CH1) domain affects antibody affinity and fine specificity, challenging the paradigm that only variable regions contribute to antigen binding. To investigate the role of the CH1 domain, we constructed IgA2 from the broadly neutralizing anti-HIV-1 2F5 IgG1, and compared 2F5 IgA2 and IgG bindin...
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.1200024109
更新日期:2012-07-31 00:00:00
abstract::A de novo mutation in the KCND2 gene, which encodes the Kv4.2 K+ channel, was identified in twin boys with intractable, infant-onset epilepsy and autism. Kv4.2 channels undergo closed-state inactivation (CSI), a mechanism by which channels inactivate without opening during subthreshold depolarizations. CSI dynamically...
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.1717082115
更新日期:2018-04-10 00:00:00
abstract::Although prairie voles (Microtus ochrogaster) are socially monogamous, males vary in both sexual and spatial fidelity. Most males form pairbonds, cohabit with one female, and defend territories. Wandering males, in contrast, have expansive home ranges that overlap many males and females. In the laboratory, pairing 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.0709116105
更新日期:2008-01-29 00:00:00
abstract::A scientist may publish tens or hundreds of papers over a career, but these contributions are not evenly spaced in time. Sixty years of studies on career productivity patterns in a variety of fields suggest an intuitive and universal pattern: Productivity tends to rise rapidly to an early peak and then gradually decli...
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.1702121114
更新日期:2017-10-31 00:00:00