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31.
Anna G. Drannik Kakon Nag Xiao-Dan Yao Bethany M. Henrick T. Blake Ball Francis A. Plummer Charles Wachihi Joshua Kimani Kenneth L. Rosenthal 《PloS one》2012,7(12)
Elafin (E) and its precursor trappin-2 (Tr) are alarm antiproteases with antimicrobial and immunomodulatory activities. Tr and E (Tr/E) have been associated with HIV-1 resistance. We recently showed that Tr/E reduced IL-8 secretion and NF-κB activation in response to a mimic of viral dsRNA and contributed to anti-HIV activity of cervicovaginal lavage fluid (CVL) of HIV-resistant (HIV-R) commercial sex workers (CSWs). Additionally, Tr, and more so E, were found to inhibit attachment/entry and transcytosis of HIV-1 in human endometrial HEC-1A cells, acting through virus or cells. Given their immunomodulatory activity, we hypothesized that Tr/E could exert anti-HIV-1 activity at multiple levels. Here, using tagged and untagged Tr/E proteins, we comparatively evaluated their protease inhibitory, anti-HIV-1, and immunomodulatory activities, and cellular distribution. E appeared to function as an autocrine/paracrine factor in HEC-1A cells, and anti-HIV-1 activity of E depended on its unmodified N-terminus and altered cellular innate activation, but not its antiprotease activity. Specifically, exogenously added N-terminus-unmodified E was able to enter the nucleus and to reduce viral attachment/entry and transcytosis, preferentially affecting R5-HIV-1ADA, but not X4-HIV-1IIIB. Further, anti-HIV-1 activity of E was associated with significantly decreased HIV-1-triggered IL-8 release, attenuated NF-κB/p65 nuclear translocation, and significantly modulated mRNA expression of innate sensors TLR3 and RIG-I in HEC-1A cells. Most importantly, we found that elevated Tr/E in CVLs of HIV-R CSWs were associated with lower mRNA levels of TLRs 2, 3, 4 and RIG-I in the genital ECs from this cohort, suggesting a link between Tr/E, HIV-1 resistance and modulated innate viral recognition in the female genital mucosa. Collectively, our data indicate that unmodified N-terminus is critical for intranuclear localization and anti-HIV-1 activity of E. We also propose that E-mediated altered cellular innate activation most likely contributes to the HIV-R phenotype of these subjects. 相似文献
32.
To manage, organize and disseminate data on the structure of biological macromolecules solved by 3D electron microscopy, an electron microscopy database has been set up at the European Bioinformatics Institute. 相似文献
33.
A model of the carbohydrate recognition domain CRD, residues 111-245, of
hamster galectin-3 has been made using homology modeling and dynamics
minimization methods. The model is based on the known x-ray structures of
bovine galectin-1 and human galectin-2. The oligosaccharides
NeuNAc-alpha2,3-Gal-beta1,4-Glc and GalNAc-alpha1, 3-
[Fuc-alpha1,2]-Gal-beta1,4-Glc, known to be specific high-affinity ligands
for galectin-3, as well as lactose recognized by all galectins were docked
in the galectin-3 CRD model structure and a minimized binding conformation
found in each case. These studies indicate a putative extended
carbohydrate-binding subsite in the hamster galectin- 3 involving Arg139,
Glu230, and Ser232 for NeuNAc-alpha2,3-; Arg139 and Glu160 for
fucose-alpha1,2-; and Arg139 and Ile141 for GalNAc-alpha1,3- substituents
on the primary galactose. Each of these positions is variable within the
whole galectin family. Two of these residues, Arg139 and Ser232, were
selected for mutagenesis to probe their importance in this newly identified
putative subsite. Residue 139 adopts main-chain dihedral angles
characteristic of an isolated bridge structural feature, while residue 232
is the C-terminal residue of beta- strand-11, and is followed immediately
by an inverse gamma-turn. A systematic series of mutant proteins have been
prepared to represent the residue variation present in the aligned
sequences of galectins-1, - 2, and -3. Minimized docked models were
generated for each mutant in complex with NeuNAc-alpha2,3-Gal-beta1,4-Glc,
GalNAc-alpha1, 3-[Fuc- alpha1,2]-Gal-beta1,4- Glc, and Gal-beta1,4-Glc.
Correlation of the computed protein-carbohydrate interaction energies for
each lectin- oligosaccharide pair with the experimentally determined
binding affinities for fetuin and asialofetuin or the relative potencies of
lactose and sialyllactose in inhibiting binding to asiolofetuin is
consistent with the postulated key importance of Arg139 in recognition of
the extended sialylated ligand.
相似文献
34.
Westbrook J Ito N Nakamura H Henrick K Berman HM 《Bioinformatics (Oxford, England)》2005,21(7):988-992
Summary: The Protein Data Bank (PDB) has recently released versionsof the PDB Exchange dictionary and the PDB archival data filesin XML format collectively named PDBML. The automated generationof these XML files is driven by the data dictionary infrastructurein use at the PDB. The correspondences between the PDB dictionaryand the XML schema metadata are described as well as the XMLrepresentations of PDB dictionaries and data files. Availability: The current software translated XML schema fileis located at http://deposit.pdb.org/pdbML/pdbx-v1.000.xsd,and on the PDB mmCIF resource page at http://deposit.pdb.org/mmcif/.PDBML files are stored on the PDB beta ftp site at ftp://beta.rcsb.org/pub/pdb/uniformity/data/XML Contact: jwest{at}rcsb.rutgers.edu 相似文献
35.
The three-dimensional environments of ligand binding sites have been derived from the parsing and loading of the PDB entries into a relational database. For each bound molecule the biological assembly of the quaternary structure has been used to determine all contact residues and a fast interactive search and retrieval system has been developed. Prosite pattern and short sequence search options are available together with a novel graphical query generator for inter-residue contacts. The database and its query interface are accessible from the Internet through a web server located at: http://www.ebi.ac.uk/msd-srv/msdsite. 相似文献
36.
Boutselakis H Dimitropoulos D Fillon J Golovin A Henrick K Hussain A Ionides J John M Keller PA Krissinel E McNeil P Naim A Newman R Oldfield T Pineda J Rachedi A Copeland J Sitnov A Sobhany S Suarez-Uruena A Swaminathan J Tagari M Tate J Tromm S Velankar S Vranken W 《Nucleic acids research》2003,31(1):458-462
The E-MSD macromolecular structure relational database (http://www.ebi.ac.uk/msd) is designed to be a single access point for protein and nucleic acid structures and related information. The database is derived from Protein Data Bank (PDB) entries. Relational database technologies are used in a comprehensive cleaning procedure to ensure data uniformity across the whole archive. The search database contains an extensive set of derived properties, goodness-of-fit indicators, and links to other EBI databases including InterPro, GO, and SWISS-PROT, together with links to SCOP, CATH, PFAM and PROSITE. A generic search interface is available, coupled with a fast secondary structure domain search tool. 相似文献
37.
Henrick Riemenschneider Qiang Guo Jakob Bader Frdric Frottin Daniel Farny Gernot Kleinberger Christian Haass Matthias Mann F. Ulrich Hartl Wolfgang Baumeister Mark S Hipp Felix Meissner Rubn FernndezBusnadiego Dieter Edbauer 《EMBO reports》2022,23(6)
Aggregation of the multifunctional RNA‐binding protein TDP‐43 defines large subgroups of amyotrophic lateral sclerosis and frontotemporal dementia and correlates with neurodegeneration in both diseases. In disease, characteristic C‐terminal fragments of ~25 kDa ("TDP‐25") accumulate in cytoplasmic inclusions. Here, we analyze gain‐of‐function mechanisms of TDP‐25 combining cryo‐electron tomography, proteomics, and functional assays. In neurons, cytoplasmic TDP‐25 inclusions are amorphous, and photobleaching experiments reveal gel‐like biophysical properties that are less dynamic than nuclear TDP‐43. Compared with full‐length TDP‐43, the TDP‐25 interactome is depleted of low‐complexity domain proteins. TDP‐25 inclusions are enriched in 26S proteasomes adopting exclusively substrate‐processing conformations, suggesting that inclusions sequester proteasomes, which are largely stalled and no longer undergo the cyclic conformational changes required for proteolytic activity. Reporter assays confirm that TDP‐25 impairs proteostasis, and this inhibitory function is enhanced by ALS‐causing TDP‐43 mutations. These findings support a patho‐physiological relevance of proteasome dysfunction in ALS/FTD. 相似文献
38.
Clive A. Henrick Jeffrey N. Labovitz Virginia L. Graves Gerardus B. Staal 《Bioorganic chemistry》1978,7(2):235-250
A number of analogs of ethyl (2E,4E)-3,7,11-trimethyl-2,4-dodecadienoate were prepared and bioassayed for juvenile hormone activity on the yellow-fever mosquito (Aedes aegypti), the greater wax moth (Galleria mellonella), the yellow mealworm (Tenebrio molitor), the house fly (Musca domestica), and the tobacco budworm (Heliothis virescens). The analog ethyl (E)-3,5-ethanol-7,11-dimethyl-2,4-dodecadienoate (VI), containing a cyclopentene ring, showed remarkable potency on the above insect species. Since this compound possesses a fixed 3-s-trans-diene conformation it may provide some insight into the active conformation of bound 2,4-dienoate analogs. 相似文献
39.
M.J. Gieselmann C.A. Henrick R.J. Anderson D.S. Moreno W.L. Roelofs 《Journal of insect physiology》1980,26(3):179-182
The California red scale, Aonidiella aurantii (Maskell), sex pheromone components were previously identified as two independently attractive norsesquiterpenes. The four possible optical isomers of one and the four possible geometric and optical isomers of the other were synthesized and tested for male California red scale attractiveness in field tests and greenhouse bioassays. The results showed that there was enantiomeric and geometric specificity and only 1 isomer of each component was significantly more active than the others. The active isomers were (3S,6R)-3-methyl-6-isopropenyl-9 decen-1-yl acetate and (3Z,6R)-3-methyl-6-isopropenyl-3,9-decadien-1-yl acetate. The presence of other isomers, including the synthetic analogue 3-methyl-6-isopropylidene-9-decen-1-yl acetate, had no effect on trap catch. 相似文献
40.
Shuchismita Dutta Kyle Burkhardt Jasmine Young Ganesh J. Swaminathan Takanori Matsuura Kim Henrick Haruki Nakamura Helen M. Berman 《Molecular biotechnology》2009,42(1):1-13
The Protein Data Bank (PDB) is the repository for three-dimensional structures of biological macromolecules, determined by
experimental methods. The data in the archive is free and easily available via the Internet from any of the worldwide centers
managing this global archive. These data are used by scientists, researchers, bioinformatics specialists, educators, students,
and general audiences to understand biological phenomenon at a molecular level. Analysis of this structural data also inspires
and facilitates new discoveries in science. This chapter describes the tools and methods currently used for deposition, processing,
and release of data in the PDB. References to future enhancements are also included.
Shuchismita Dutta, Kyle Burkhardt, and Ganesh J. Swaminathan have contributed equally to this work. 相似文献