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排序方式: 共有93条查询结果,搜索用时 15 毫秒
71.
72.
Bodill T Conibear AC Blatch GL Lobb KA Kaye PT 《Bioorganic & medicinal chemistry》2011,19(3):1321-1327
The diethyl esters and disodium salts of a range of heteroarylcarbamoylphosphonic acids have been prepared and evaluated as analogues of the highly active DOXP-reductoisomerase (DXR) inhibitor, fosmidomycin. Computer-simulated docking studies, Saturation Transfer Difference (STD) NMR analysis and enzyme inhibition assays have been used to explore enzyme-binding and -inhibition potential, while in silico analysis of the DXR active site has highlighted the importance of including a well-parameterised metal co-factor in docking studies and has revealed the availability of an additional binding pocket to guide future drug design. 相似文献
73.
Appu Kumar Singh Babu Manjasetty Balasubramani GL Sukirte Koul Abhishek Kaushik Mary Krishna Ekka Vijay Singh S. Kumaran 《PloS one》2015,10(5)
Fad35R from Mycobacterium tuberculosis binds to the promoter site of Fad35 operon and its DNA binding activities are reduced in the presence of tetracycline and palmitoyl-CoA. We resolved the crystal structure of Fad35R using single-wavelength anomalous diffraction method (SAD). Fad35R comprises canonical DNA binding domain (DBD) and ligand binding domain (LBD), but displays several distinct structural features. Two recognition helices of two monomers in the homodimer are separated by ~ 48 Å and two core triangle-shaped ligand binding cavities are well exposed to solvent. Structural comparison with DesT and QacR structures suggests that ligand binding-induced movement of α7, which adopts a straight conformation in the Fad35R, may be crucial to switch the conformational states between repressive and derepressive forms. Two DBDs are packed asymmetrically, creating an alternative dimer interface which coincides with the possible tetramer interface that connects the two canonical dimers. Quaternary state of alternative dimer mimics a closed-state structure in which two recognition helices are distanced at ~ 35 Å and ligand binding pockets are inaccessible. Results of biophysical studies indicate that Fad35R has the propensity to oligomerize in solution in the presence of tetracycline. We present the first structure of a FadR homologue from mycobacterium and the structure reveals DNA and ligand binding features of Fad35R and also provides a view on alternative quaternary states that mimic open and closed forms of the regulator. 相似文献
74.
Cockburn IL Pesce ER Pryzborski JM Davies-Coleman MT Clark PG Keyzers RA Stephens LL Blatch GL 《Biological chemistry》2011,392(5):431-438
Plasmodium falciparum heat shock protein 70 (PfHsp70-1) is thought to play an essential role in parasite survival and virulence in the human host, making it a potential antimalarial drug target. A malate dehydrogenase based aggregation suppression assay was adapted for the screening of small molecule modulators of Hsp70. A number of small molecules of natural (marine prenylated alkaloids and terrestrial plant naphthoquinones) and related synthetic origin were screened for their effects on the protein aggregation suppression activity of purified recombinant PfHsp70-1. Five compounds (malonganenone A-C, lapachol and bromo-β-lapachona) were found to inhibit the chaperone activity of PfHsp70-1 in a concentration dependent manner, with lapachol preferentially inhibiting PfHsp70-1 compared to another control Hsp70. Using growth inhibition assays on P. falciparum infected erythrocytes, all of the compounds, except for malonganenone B, were found to inhibit parasite growth with IC(50) values in the low micromolar range. Overall, this study has identified two novel classes of small molecule inhibitors of PfHsp70-1, one representing a new class of antiplasmodial compounds (malonganenones). In addition to demonstrating the validity of PfHsp70-1 as a possible drug target, the compounds reported in this study will be potentially useful as molecular probes for fundamental studies on Hsp70 chaperone function. 相似文献
75.
Linksvayer TA Kaftanoglu O Akyol E Blatch S Amdam GV Page RE 《Journal of evolutionary biology》2011,24(9):1939-1948
Social evolution in honey bees has produced strong queen-worker dimorphism for plastic traits that depend on larval nutrition. The honey bee developmental programme includes both larval components that determine plastic growth responses to larval nutrition and nurse components that regulate larval nutrition. We studied how these two components contribute to variation in worker and queen body size and ovary size for two pairs of honey bee lineages that show similar differences in worker body-ovary size allometry but have diverged over different evolutionary timescales. Our results indicate that the lineages have diverged for both nurse and larval developmental components, that rapid changes in worker body-ovary size allometry may disrupt queen development and that queen-worker dimorphism arises mainly from discrete nurse-provided nutritional environments, not from a developmental switch that converts variable nutritional environments into discrete phenotypes. Both larval and nurse components have likely contributed to the evolution of queen-worker dimorphism. 相似文献
76.
Mutsvunguma LZ Moetlhoa B Edkins AL Luke GA Blatch GL Knox C 《Cell stress & chaperones》2011,16(5):505-515
Theiler’s murine encephalomyelitis virus (TMEV) is a positive-sense RNA virus belonging to the Cardiovirus genus in the family Picornaviridae. In addition to other host cellular factors and pathways, picornaviruses utilise heat
shock proteins (Hsps) to facilitate their propagation in cells. This study investigated the localisation of Hsps 70 and 90
in TMEV-infected BHK-21 cells by indirect immunofluorescence and confocal microscopy. The effect of Hsp90 inhibitors novobiocin
(Nov) and geldanamycin (GA) on the development of cytopathic effect (CPE) induced by infection was also examined. Hsp90 staining
was uniformly distributed in the cytoplasm of uninfected cells but was found concentrated in the perinuclear region during
late infection where it overlapped with the signal for non-structural protein 2C within the viral replication complex. Hsp70
redistributed into the vicinity of the viral replication complex during late infection, but its distribution did not overlap
with that of 2C. Inhibition of Hsp90 by GA and Nov had a negative effect on virus growth over a 48-h period as indicated by
no observable CPE in treated compared to untreated cells. 2C was detected by Western analysis of GA-treated infected cell
lysates at doses between 0.01 and 0.125 μM, suggesting that processing of viral precursors was not affected in the presence
of this drug. In contrast, 2C was absent in cell lysates of Nov-treated cells at doses above 10 μM, although CPE was evident
48 hpi. This is the first study describing the dynamic behaviour of Hsps 70 and 90 in TMEV-infected cells and to identify
Hsp90 as an important host factor in the life cycle of this virus. 相似文献
77.
Abstract: A decapod crustacean faunule from the lower Miocene (upper Burdigalian, ‘Karpatian’) of the Slovakian part of the Vienna Basin comprise five new species: Callianopsis marianae (Ctenochelidae), Crosniera schweitzerae (Thomassiniidae), Agononida cerovensis and Munidopsis lieskovensis (both Galatheidae) plus Mursia harnicari (Calappidae). The new species of Callianopsis is the first undoubted member of the genus to be recorded from Europe; it is based on sexually dimorphic major and minor chelae as well as on portions of carapace and abdomen. Crosniera schweitzerae sp. nov. and Agononida cerovensis sp. nov. constitute the first fossil members of these genera. Additional material of an enigmatic crab, Styrioplax exiguus, and a re‐examination of the type material, confirms assignment of that genus to the subfamily Rhizopinae (family Pilumnidae). Palaeoecological data suggest that deposition of the levels (Lak?árska Nová Ves Formation) from which these taxa were collected took place under generally low‐energy, deep‐water conditions that were conducive to the preservation of delicate structures. Palaeobiogeographical affinities of the described taxa suggest a trans‐Atlantic migration during the early Miocene. 相似文献
78.
Ingrid GL van de Port Lotte Wevers Hanneke Roelse Lenneke van Kats Eline Lindeman Gert Kwakkel 《BMC neurology》2009,9(1):43
Background
Most patients who suffer a stroke experience reduced walking competency and health-related quality of life (HRQoL). A key factor in effective stroke rehabilitation is intensive, task-specific training. Recent studies suggest that intensive, patient-tailored training can be organized as a circuit with a series of task-oriented workstations. 相似文献79.
Cassandra A. Louw Michael H. Ludewig Jens Mayer Gregory L. Blatch 《Parasitology international》2010,59(4):497-505
Proteins belonging to the Hsp70 class of molecular chaperones are highly conserved and ubiquitous, performing an essential role in the maintenance of cellular homeostasis in almost all known organisms. Trypanosoma brucei, Trypanosoma cruzi and Leishmania major are human parasites collectively known as the Tritryps. The Tritryps undergo extensive morphological changes during their life cycles, largely triggered by the marked differences between conditions in their insect vector and human host. Hsp70s are synthesised in response to these marked changes in environment and are proposed to be required for these parasites to successfully transition between differentiation stages while remaining viable and infective. While the Tritryps Hsp70 complement consists of homologues of all the major eukaryotic Hsp70s, there are a number of novel members, and some unique structural features. This review critically evaluates the current knowledge on the Tritryps Hsp70 proteins with an emphasis on T. brucei, and highlights some novel and previously unstudied aspects of these multifaceted molecular chaperones. 相似文献
80.
Sinclair BJ Terblanche JS Scott MB Blatch GL Jaco Klok C Chown SL 《Journal of insect physiology》2006,52(1):29-50
The environmental physiology of three speciesof Collembola: Cryptopygus cisantarcticus, Isotoma klovstadi (Isotomidae) and Friesea grisea (Neanuridae) was investigated from November 2002 to February 2003 at Cape Hallett, North Victoria Land, Antarctica. All three species were freeze avoiding, and while supercooling points were variable on seasonal and daily scales in I. klovstadi and C. cisantarcticus, they remained largely static in F. grisea. LT50 (temperature where 50% of animals are killed by cold) was -13.6, -19.1 and -19.8 degrees C for C. cisantarcticus, I. klovstadi and F. grisea, respectively. Upper lethal temperature was 34, 34 and 38 degrees C for C. cisantarcticus, I. klovstadi and F. grisea. Critical thermal minimum onset (the temperature where individuals entered chill coma) was ca. -7, -12 and -8 degrees C for C. cisantarcticus, I. klovstadi and F. grisea, and 25% of I. klovstadi individuals froze without entering chill coma. Critical thermal maximum (the onset of spasms at high temperature) was 30, 33 and 34 degrees C for C. cisantarcticus, I. klovstadi and F. grisea. Haemolymph osmolality was approximately 720 mOsm for C. cisantarcticus and 680 mOsm for I. klovstadi, and both species showed a moderate degree of thermal hysteresis, which persisted through the season. Desiccation resistance was measured as survival above silica gel, and the species survived in the rank order of C. cisantarcticus< I. klovstadi = F. grisea. Desiccation resulted in an increase in haemolymph osmolality in I. klovstadi, and water was quickly regained by desiccation-stressed individuals that had access to liquid water, but not by individuals placed in high humidity, indicating that this species is unable to absorb atmospheric water vapour. SDS-PAGE did not suggest any strong patterns in protein synthesis either seasonally or in response to temperature or desiccation stress. Microclimate temperatures were measured at sites representative of collection sites for the three species. Microclimate temperatures were highly variable on a diurnal and weekly scale (the latter relating to weather patterns), but showed little overall variation across the summer season. Potentially lethal high and low temperatures were recorded at several sites, and it is suggested that these temperature extremes account for the observed restriction of the less-tolerant C. cisantarcticus at Cape Hallett. Together, these data significantly increase the current knowledge of the environmental physiology of Antarctic Collembola. 相似文献