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991.
Chemosensory proteins in the honey bee: Insights from the annotated genome, comparative analyses and expressional profiling 总被引:5,自引:0,他引:5
Small chemosensory proteins (CSPs) belong to a conserved, but poorly understood protein family that has been implicated in transporting chemical stimuli within insect sensilla. However, their expression patterns suggest that these molecules are also critical for other functions including early development. Here we used both bioinformatics and experimental approaches to characterize the CSP gene family in a social insect, the Western honey bee Apis mellifera, and then compared its members to CSPs in other arthropods. The number of CSPs in the honey bee genome (six) is similar to that found in the sequenced dipteran species (four-seven), but is much lower than the number of CSPs in the moth or in the beetle (around 20 each). These differences seem to be the result of lineage specific expansions. Our analysis of CSPs in a number of arthropods reveals a conserved gene family found in both Mandibulates and Chelicerates. Expressional profiling in diverse tissues and throughout development reveals broader than expected patterns of expression with none of the CSPs restricted to the antennae and one found only in the queen ovaries and in embryos. We conclude that CSPs are multifunctional context-dependent proteins involved in diverse cellular processes ranging from embryonic development to chemosensory signal transduction. Some CSPs may function in cuticle synthesis, consistent with their evolutionary origins in the arthropods. 相似文献
992.
Differential regulation of mouse equilibrative nucleoside transporter 1 (mENT1) splice variants by protein kinase CK2 总被引:1,自引:0,他引:1
Nucleosides are accumulated by cells via a family of equilibrative transport proteins (ENTs). An alternative splice variant of the most common subtype of mouse ENT (ENT1) has been identified which is missing a protein kinase CK2 (casein kinase 2) consensus site (Ser(254)) in the central intracellular loop of the protein. We hypothesized that this variant (mENT1a) would be less susceptible to modulation by CK2-mediated phosphorylation compared to the variant containing the serine at position 254 (mENT1b). Each splice variant was transfected into nucleoside transporter deficient PK15 cells, and stable transfectants assessed for their ability to bind the ENT1-selective probe [(3)H]nitrobenzylthioinosine (NBMPR) and to mediate the cellular uptake of [(3)H]2-chloroadenosine, with or without treatment with the CK2 selective inhibitor, 4,5,6,7-tetrabromobenzotriazole (TBB). mENT1a had a higher affinity for NBMPR relative to mENT1b - measured both directly by the binding of [(3)H]NBMPR, and indirectly via inhibition of [(3)H]2-chloroadenosine influx by NBMPR. Furthermore, incubation of mENT1b-expressing cells with 10 microM TBB for 48 h decreased both the K(D) and B(max) of [(3)H]NBMPR binding, as well as the V(max) of 2-chloroadenosine uptake, whereas similar treatment of mENT1a-expressing cells with TBB had no effect. PK15 cells transfected with hENT1, which has Ser(254), was similar to mENT1b in its response to TBB. In conclusion, inhibition of CK2 activity, or deletion of Ser(254) from mENT1, enhances transporter affinity for the inhibitor, NBMPR, and reduces the number of ENT1 proteins functioning at the level of the plasma membrane. 相似文献
993.
X-ray crystallography of biologically important RNA molecules has been hampered by technical challenges, including finding heavy-atom derivatives to obtain high-quality experimental phase information. Existing techniques have drawbacks, limiting the rate at which important new structures are solved. To address this, we have developed a reliable means to localize heavy atoms specifically to virtually any RNA. By solving the crystal structures of thirteen variants of the G*U wobble pair cation binding motif, we have identified a version that when inserted into an RNA helix introduces a high-occupancy cation binding site suitable for phasing. This "directed soaking" strategy can be integrated fully into existing RNA crystallography methods, potentially increasing the rate at which important structures are solved and facilitating routine solving of structures using Cu-Kalpha radiation. This method already has been used to solve several crystal structures. 相似文献
994.
Flynn GE Black KD Islas LD Sankaran B Zagotta WN 《Structure (London, England : 1993)》2007,15(6):671-682
Hyperpolarization-activated cyclic nucleotide-modulated (HCN) ion channels regulate the spontaneous firing activity and electrical excitability of many cardiac and neuronal cells. The modulation of HCN channel opening by the direct binding of cAMP underlies many physiological processes such as the autonomic regulation of the heart rate. Here we use a combination of X-ray crystallography and electrophysiology to study the allosteric mechanism for cAMP modulation of HCN channels. SpIH is an invertebrate HCN channel that is activated fully by cAMP, but only partially by cGMP. We exploited the partial agonist action of cGMP on SpIH to reveal the molecular mechanism for cGMP specificity of many cyclic nucleotide-regulated enzymes. Our results also elaborate a mechanism for the allosteric conformational change in the cyclic nucleotide-binding domain and a mechanism for partial agonist action. These mechanisms will likely extend to other cyclic nucleotide-regulated channels and enzymes as well. 相似文献
995.
Dysferlin and muscle membrane repair 总被引:2,自引:0,他引:2
The ability to repair membrane damage is conserved across eukaryotic cells and is necessary for the cells to survive a variety of physiological and pathological membrane disruptions. Membrane repair is mediated by rapid Ca(2+)-triggered exocytosis of various intracellular vesicles, such as lysosomes and enlargeosomes, which lead to the formation of a membrane patch that reseals the membrane lesion. Recent findings suggest a crucial role for dysferlin in this repair process in muscle, possibly as a Ca(2+) sensor that triggers vesicle fusion. The importance of membrane repair is highlighted by the genetic disease, dysferlinopathy, in which the primary defect is the loss of Ca(2+)-regulated membrane repair due to dysferlin deficiency. Future research on dysferlin and its interacting partners will enhance the understanding of this important process and provide novel avenues to potential therapies. 相似文献
996.
Wu-Yang Huang Yi-Zhong Cai Kevin D. Hyde Harold Corke Mei Sun 《World journal of microbiology & biotechnology》2007,23(9):1253-1263
Diverse endophytic fungi exist within plant aerial tissues, with a global estimate of up to a million undescribed species.
These endophytes constitute a rich bio-resource for exploration to discover new natural products. Here we investigate fungal
endophytes associated with a medicinal plant, Nerium oleander L. (Apocynaceae). A total of 42 endophytic fungal strains were isolated from the host plant. Total antioxidant capacity,
xanthine oxidase inhibitory activity, antimicrobial activity, and total phenolic content (TPC) were evaluated for 16 representative
fungal cultures grown in improved Czapek’s broth and for the host plant. The total antioxidant capacities and phenolic contents
of the fungal cultures ranged from 9.59 to 150.79 μmol trolox/100 mL culture, and from 0.52 to 13.95 mg gallic acid/100 mL
culture, respectively. The fungal culture of an endophytic strain Chaetomium sp. showed the strongest antioxidant capacity, contained the highest level of phenolics, and to some extent inhibited xanthine
oxidase activity with an IC50 value of 109.8 μg/mL. A significant positive correlation was found between antioxidant capacity and TPC in the tested samples.
Most of the endophytic fungal cultures tested have a wide range of antimicrobial activities, which were not very strong, but
much better than those of the host plant. The major bioactive constituents of the fungal cultures were investigated using
LC-ESI-MS and GC-MS, and preliminary identification detected phenolics (e.g. phenolic acids and their derivatives, flavonoids)
and volatile and aliphatic compounds. This study shows that the endophytic fungi isolated from N. oleander can be a potential antioxidant resource. 相似文献
997.
The pathogenic yeast Candida albicans produces large N-glycans with outer regions containing only mannose residues. The outer region comprises a primary branch with multiple secondary and tertiary branches. Tertiary branches are linked to secondary branches by phosphodiester bridges. In the current model of outer chain elongation in the genetically related yeast Saccharomyces cerevisiae, synthesis of the branches occurs sequentially, primary to tertiary. Thus, disruption of mannosylphosphorylation, the initial step in tertiary branch formation, should not affect primary or secondary branch production. Compared to its wild-type parent, a C. albicans mutant defective in tertiary branch mannosylphosphorylation (mnn4Delta/mnn4Delta) made outer regions with reduced susceptibility to low acid acetolysis treatment, suggesting that the secondary or primary region had been modified. Higher acid acetolysis conditions were required to release the secondary branches from the primary branches. The released secondary branches constitute the subset of the wild-type secondary branches that lack a phosphate group. In contrast, the acid-stable region of both wild-type and mnn4Delta S. cerevisiae strains required high acid acetolysis conditions to release the secondary branches, despite having smaller and less complex secondary and tertiary branches. These results suggest that the complex and longer secondary and tertiary branches of C. albicans affect the conformation of the acid-stable region to render it more susceptible to acetolysis which implies secondary and tertiary branch formation in C. albicans are interdependent events and occur concurrently, rather than sequentially. 相似文献
998.
Barrett DG Catalano JG Deaton DN Long ST McFadyen RB Miller AB Miller LR Samano V Tavares FX Wells-Knecht KJ Wright LL Zhou HQ 《Bioorganic & medicinal chemistry letters》2007,17(1):22-27
Starting from a potent ketone-based inhibitor with poor drug properties, incorporation of P(2)-P(3) elements from a ketoamide-based inhibitor led to the identification of a hybrid series of ketone-based cathepsin K inhibitors with better oral bioavailability than the starting ketone. 相似文献
999.
DeCarr LB Buckholz TM Coish PD Fathi Z Fisk SE Mays MR O'Connor SJ Lumb KJ 《Bioorganic & medicinal chemistry letters》2007,17(2):538-541
Activation of the NPY2 receptor to reduce appetite while avoiding stimulation of the NPY1 and NPY5 receptors that induce feeding provides a pharmaceutical approach to modulate food intake. The naturally occurring peptide PYY(3-36) is a nonselective NPY1, NPY2, and NPY5 agonist. N-terminal truncation of PYY to abrogate affinity for the NPY1 and NPY5 receptors and subsequent N-terminal modification with aminobenzoic analogs to restore NPY2 receptor potency results in a series of highly selective NPY2 receptor peptide agonists. 相似文献
1000.
Alhamadsheh MM Waters NC Huddler DP Kreishman-Deitrick M Florova G Reynolds KA 《Bioorganic & medicinal chemistry letters》2007,17(4):879-883
A series of cyclic sulfones has been synthesized and their activity against beta-ketoacyl-ACP-synthase III (FabH) has been investigated. The compounds are selectively active against Escherichia coli FabH (ecFabH), but not Mycobacterium tuberculosis FabH (mtFabH) or Plasmodium falciparum KASIII (PfKASIII). The activity against ecFabH ranges from 0.9 to >100microM and follows a consistent general SAR trend. Many of the compounds were shown to have antimalarial activity against chloroquine (CQ)-sensitive (D6) P. falciparum (IC(50)=5.3microM for the most potent inhibitor) and some were active against E. coli (MIC=6.6microg/ml for the most potent inhibitor). 相似文献