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131.
The 3-D structure of the human mTOR kinase domain was modeled based on the crystal structure of PI3Kγ using comparative modeling
methods, and the ATP-binding site of mTOR was characterized. The mTOR kinase 3-D model structure is similar to the structure
of the PI3Kγ kinase domain, and exhibits great similarity to PI3Kγ at the active site of the kinase. Pharmacophore generation,
the docking of mTOR inhibitors, and molecular dynamics (MD) simulations of mTOR–inhibitor docked complexes were carried out
in this work. The best pharmacophore model generated from 27 ATP-competitive mTOR inhibitors comprised two hydrogen-bond acceptors,
one aromatic ring, and one hydrophobic feature. These 27 inhibitors were docked into the ATP-binding site comprising the DFG
motif, and the interactions in each protein–inhibitor complex were characterized. Mapping the pharmacophore model onto the
docked inhibitors explained the specificity of the features of the pharmacophore and how they were arranged inside the active
site of mTOR kinase. MD studies revealed important structural features, such as the large hydrophobic pocket “HP” and hydrophilic
pocket “A1,” and the solvent-exposed hydrophilic pocket “A2” at the active site of mTOR. Our results provide structural models
of mTOR–inhibitor complexes and clues that should aid in the design of better mTOR kinase inhibitors. 相似文献
132.
In Ti02 nanostructured dye-sensitized solar cells indole based organic dyes D149, D205 exhibits greater power conversion efficiency.
Such organic dye molecules are easily undergone for aggregation. Aggregation in dye molecules leads to reduce electron transfer
process in dye-sensitized solar cells. Therefore, anti-aggregating agents such as chenodeoxycholic acid are commonly added
to organic dye solution in DSSCs. Studying aggregation of such dye molecules in the absence of semiconductors gives a detailed
influence of anti-aggregating agents on dye molecules. Atomistic level of molecular dynamics (MD) simulations were performed
on aggregation of indole type dye molecules D149, D205 and D205-F with anti-aggregating agent chenodeoxy cholic acid using
AMBER program. The trajectories of the MD simulations were analyzed with order parameters such as radial atom pair distribution
functions g(r), diffusion coefficients and root mean square deviations values. MD results suggest that addition of chenodeoxy
cholic acid to dyes significantly reduces structural arrangement and increases conformational flexibility and mobility of
dye molecules. The influence of semi-perfluorinated alkyl chains in indole dye molecules was analyzed. The parameters such
as open-circuit voltage (Voc) and power conversion efficiency (η) of dye-sensitized solar cells are corroborated with flexibility and diffusion values
of dye molecules. 相似文献
133.
134.
Cloning of an ovule specific promoter from Arabidopsis thaliana and expression of beta-glucuronidase
Nain V Verma A Kumar N Sharma P Ramesh B Kumar PA 《Indian journal of experimental biology》2008,46(4):207-211
Tissue specific expression of transgenes in plant species has several advantages over constitutive expression. Identification of ovule specific promoters would be useful in genetic engineering of plants with a variety of desirable traits such as genetically engineered parthenocarpy, female sterile plants or seedless fruits. Relative inaccessibility and difficulty in harvesting adequate amounts of tissue at known developmental stages has impeded the progress in cloning of promoters involved in ovule development. In the present study an ovule specific promoter was cloned from Arabidopsis AGL11 gene and used to express GUS (beta-glucuronidase) gene in transgenic Arabidopsis. Histochemical staining of GUS appeared in the center of young ovary (ovules), but no detectable GUS activity was observed in vegetative plant tissues, sepals, petals and androecium. AGL11 gene promoter can be useful to modify the developmental path of plants by expressing either plant hormones or lethal genes for agronomic purpose. 相似文献
135.
Christeller JT Farley PC Marshall RK Anandan A Wright MM Newcomb RD Laing WA 《Journal of molecular evolution》2006,63(6):747-757
The squash (Cucurbita maxima) phloem exudate-expressed aspartic proteinase inhibitor (SQAPI) is a novel aspartic acid proteinase inhibitor, constituting
a fifth family of aspartic proteinase inhibitors. However, a comparison of the SQAPI sequence to the phytocystatin (a cysteine
proteinase inhibitor) family sequences showed ∼30% identity. Modeling SQAPI onto the structure of oryzacystatin gave an excellent
fit; regions identified as proteinase binding loops in cystatin coincided with regions of SQAPI identified as hypervariable,
and tryptophan fluorescence changes were also consistent with a cystatin structure. We show that SQAPI exists as a small gene
family. Characterization of mRNA and clone walking of genomic DNA (gDNA) produced 10 different but highly homologous SQAPI
genes from Cucurbita maxima and the small family size was confirmed by Southern blotting, where evidence for at least five loci was obtained. Using primers
designed from squash sequences, PCR of gDNA showed the presence of SQAPI genes in other members of the Cucurbitaceae and in
representative members of Coriariaceae, Corynocarpaceae, and Begoniaceae. Thus, at least four of seven families of the order
Cucurbitales possess member species with SQAPI genes, covering ∼99% of the species in this order. A phylogenetic analysis
of these Cucurbitales SQAPI genes indicated not only that SQAPI was present in the Cucurbitales ancestor but also that gene
duplication has occurred during evolution of the order. Phytocystatins are widespread throughout the plant kingdom, suggesting
that SQAPI has evolved recently from a phytocystatin ancestor. This appears to be the first instance of a cystatin being recruited
as a proteinase inhibitor of another proteinase family.
[Reviewing Editor: Dr. Antony Dean] 相似文献
136.
The vesicular acetylcholine transporter (VAChT) contains six conserved sequence motifs that are rich in proline and glycine. Because these residues can have special roles in the conformation of polypeptide backbone, the motifs might have special roles in conformational changes during transport. Using published bioinformatics insights, the amino acid sequences of the 12 putative, helical, transmembrane segments of wild-type and mutant VAChTs were analyzed for propensity to form non-alpha-helical conformations and molecular notches. Many instances were found. In particular, high propensity for kinks and notches are robustly predicted for motifs D2, C and C'. Mutations in these motifs either increase or decrease Vmax for transport, but they rarely affect the equilibrium dissociation constants for ACh and the allosteric inhibitor, vesamicol. The near absence of equilibrium effects implies that the mutations do not alter the backbone conformation. In contrast, the Vmax effects demonstrate that the mutations alter the difficulty of a major conformational change in transport. Interestingly, mutation of an alanine to a glycine residue in motif C significantly increases the rates for reorientation across the membrane. These latter rates are deduced from the kinetics model of the transport cycle. This mutation is also predicted to produce a more flexible kink and tighter tandem notches than are present in wild-type. For the full set of mutations, faster reorientation rates correlate with greater predicted propensity for kinks and notches. The results of the study argue that conserved motifs mediate conformational changes in the VAChT backbone during transport. 相似文献
137.
138.
Patterns of fungal colonization, mass loss and biochemical changes during the decomposition of predried and fresh (naturally
fallen) leaves of Rhizophora mucronata were studied in a southwest mangrove of India. Dried and fresh leaves in litter bags were introduced at the mid-tide zone
and retrieved after 1, 2, 4, 8, 10, 12 and 14 weeks. On incubation in the laboratory, a total of 5 ascomycetes and 18 anamorphic
fungi were recorded. The majority of anamorphic taxa were natural inhabitants of the phyllosphere of senescent leaves. Following
two weeks of exposure, they were largely replaced by marine fungi (ascomycetes and anamorphic fungi). More taxa were recovered
from dried than from fresh leaves, and predrying accelerated the initial rate of mass loss. Ergosterol levels were much lower
than those reported from vascular plant detritus exposed in other aquatic habitats. Both ergosterol and nitrogen levels peaked
after between 4 weeks and 8 weeks of exposure; ergosterol levels subsequently declined, while nitrogen remained stable in
predried leaves and fell in fresh leaves. The dynamics of remaining mass for the first 8 weeks of exposure were best described
by a double-exponential decay model. The decay rate then appeared to accelerate, and the second phase was best described by
a single exponential decay model. The apparent breakpoint coincided with an increase in the salinity of the mangrove swamp. 相似文献
139.
Guruprasad R. Medigeshi Maria Krikunova Karthikeyan Radhakrishnan Dirk Wenzel Jürgen Klingauf Peter Schu 《Traffic (Copenhagen, Denmark)》2008,9(1):121-132
The adaptor protein complex AP-1 mediates vesicular protein sorting between the trans Golgi network and endosomes. AP-1 recycles between membranes and the cytoplasm together with clathrin during transport vesicle formation and vesicle uncoating. AP-1 recycles independent of clathrin, indicating binding to unproductive membrane domains and premature termination of vesicle budding. Membrane recruitment requires ADP ribosylation factor-1-GTP, a transmembrane protein containing an AP-1-binding motif and phosphatidyl-inositol phosphate (PI-4-P). Little is known about the regulation of AP-1 membrane–cytoplasm recycling. We identified the N-terminal domain of μ1A-adaptin as being involved in the regulation of AP-1 membrane–cytoplasm recycling by constructing chimeras of μ1A and its homologue μ2. The AP-1* complex containing this μ2–μ1A chimera had slowed down recycling kinetics, resulting in missorting of mannose 6-phosphate receptors. The N-terminal domain is only accessible from the cytoplasmic AP-1 surface. None of the proteins known to influence AP-1 membrane recycling bound to this μ1A domain, indicating the regulation of AP-1 membrane–cytoplasm recycling by an yet unidentified cytoplasmic protein. 相似文献
140.