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91.
Versha Rai Antresh Kumar Sneha Sudha Komath Rajendra Prasad 《生物化学与生物物理学报:生物膜》2008,1778(10):2143-2153
Although essentially conserved, the N-terminal nucleotide-binding domain (NBD) of Cdr1p and other fungal transporters has some unique substitutions of amino acids which appear to have functional significance for the drug transporters. We have previously shown that the typical Cys193 in Walker A as well as Trp326 and Asp327 in the Walker B of N-terminal NBD (NBD-512) of Cdr1p has acquired unique roles in ATP binding and hydrolysis. In the present study, we show that due to spatial proximity, fluorescence resonance energy transfer (FRET) takes place between Trp326 of Walker B and MIANS [2-(4-maleimidoanilino) naphthalene-6-sulfonic acid] on Cys193 of Walker A motif. By exploiting FRET, we demonstrate how these critical amino acids are positioned within the nucleotide-binding pocket of NBD-512 to bind and hydrolyze ATP. Our results show that both Mg2+ coordination and nucleotide binding contribute to the formation of the active site. The entry of Mg2+ into the active site causes the first large conformational change that brings Trp326 and Cys193 in close proximity to each other. We also show that besides Trp326, typical Glu238 in the Q-loop also participates in coordination of Mg2+ by NBD-512. A second conformational change is induced when ATP, but not ADP, docks into the pocket. Asn328 does sensing of the γ-phosphate of the substrate in the extended Walker B motif, which is essential for the second conformational change that must necessarily precede ATP hydrolysis. Taken together our results imply that the uniquely placed residues in NBD-512 have acquired critical roles in ATP catalysis, which drives drug extrusion. 相似文献
92.
Plants are a nearly unlimited source of phytochemicals. The plants produce various secondary metabolites, which are useful in its interaction with the environment, various stress factors and development of resistance against pathogen attack. A wide array of external stimuli are capable of triggering changes in the plant cell which leads to a cascade of reactions, ultimately resulting in the formation and accumulation of secondary metabolites which helps the plant to overcome the stress factors. The biotic and abiotic elicitors can result in an enhancement of the secondary metabolite production. The stimuli are perceived by receptors, which then result in the activation of the secondary messengers. These then transmit the signals into the cell through the signal transduction pathways leading to gene expression and biochemical changes. There is interplay of the signaling molecules also which regulates the entire pathway. This review is oriented towards the factors, which influence signal transduction pathway(s) with special reference to polyamines, calcium, jasmonates, salicylates, nitric oxide and ethylene. The interplay of these components to elicit a defense response is discussed. Molecular aspects of disease resistance and regulation of plant secondary metabolism has also been presented. 相似文献
93.
Entamoeba dispar andEntamoeba histolytica are now recognized as two distinct species-the former being nonpathogenic to humans. We had earlier studied the organization
of ribosomal RNA genes inE. histolytica. Here we report the analysis of ribosomal RNA genes inE. dispar. The rRNA genes ofE. dispar, like their counterpart inE. histolytica are located on a circular rDNA molecule. From restriction map analysis, the size ofE. dispar rDNA circle was estimated to be 24·4 kb. The size was also confirmed by linearizing the circle withBsaHI, and by limited DNAseI digestion. The restriction map of theE. dispar rDNA circle showed close similarity to EhR1, the rDNA circle ofE. histolytica strain HM-1:IMSS which has two rDNA units per circle. The various families of short tandem repeats found in the upstream
and downstream intergenic spacers (IGS) of EhR1 were also present inE. dispar. Partial sequencing of the cloned fragments ofE. dispar rDNA and comparison with EhR1 revealed only 2·6% to 3·8% sequence divergence in the IGS. The region Tr and the adjoiningPvuI repeats in the IGS of EhR1, which are missing in thoseE. histolytica strains that have one rDNA unit per circle, were present in theE. dispar rDNA circle. Such close similarity in the overall organization and sequence of the IGS of rDNAs of two different species
is uncommon. In fact the spacer sequences were only slightly more divergent than the 18S rRNA gene sequence which differs
by 1·6% in the two species. The most divergent sequence betweenE. histolytica andE. dispar was the internal transcribed spacer, ITS2. Therefore, it was concluded that probes derived from the ITS1 and ITS 2 sequences
would be more reliable and reproducible than probes from the IGS regions used earlier for identifying these species. 相似文献
94.
Phanindra Velisetty Sreevatsa V. Chalamalasetti Sudha Chakrapani 《The Journal of biological chemistry》2014,289(5):3013-3025
Ligand binding at the extracellular domain of pentameric ligand-gated ion channels initiates a relay of conformational changes that culminates at the gate within the transmembrane domain. The interface between the two domains is a key structural entity that governs gating. Molecular events in signal transduction at the interface are poorly defined because of its intrinsically dynamic nature combined with functional modulation by membrane lipid and water vestibules. Here we used electron paramagnetic resonance spectroscopy to delineate protein motions underlying Gloeobacter violaceus ligand-gated ion channel gating in a membrane environment and report the interface conformation in the closed and the desensitized states. Extensive intrasubunit interactions were observed in the closed state that are weakened upon desensitization and replaced by newer intersubunit contacts. Gating involves major rearrangements of the interfacial loops, accompanied by reorganization of the protein-lipid-water interface. These structural changes may serve as targets for modulation of gating by lipids, alcohols, and amphipathic drug molecules. 相似文献
95.
96.
The scarcity of rural doctors has undermined the ability of health systems in low and middle-income countries like India to provide quality services to rural populations. This study examines job preferences of doctors and nurses to inform what works in terms of rural recruitment strategies. Job acceptance of different strategies was compared to identify policy options for increasing the availability of clinical providers in rural areas. In 2010 a Discrete Choice Experiment was conducted in India. The study sample included final year medical and nursing students, and in-service doctors and nurses serving at Primary Health Centers. Eight job attributes were identified and a D-efficient fractional factorial design was used to construct pairs of job choices. Respondent acceptance of job choices was analyzed using multi-level logistic regression. Location mattered; jobs in areas offering urban amenities had a high likelihood of being accepted. Higher salary had small effect on doctor, but large effect on nurse, acceptance of rural jobs. At five times current salary levels, 13% (31%) of medical students (doctors) were willing to accept rural jobs. At half this level, 61% (52%) of nursing students (nurses) accepted a rural job. The strategy of reserving seats for specialist training in exchange for rural service had a large effect on job acceptance among doctors, nurses and nursing students. For doctors and nurses, properly staffed and equipped health facilities, and housing had small effects on job acceptance. Rural upbringing was not associated with rural job acceptance. Incentivizing doctors for rural service is expensive. A broader strategy of substantial salary increases with improved living, working environment, and education incentives is necessary. For both doctors and nurses, the usual strategies of moderate salary increases, good facility infrastructure, and housing will not be effective. Non-physician clinicians like nurse-practitioners offer an affordable alternative for delivering rural health care. 相似文献
97.
Vaideeswaran Sivasakthi Parimelzaghan Anitha Kalavathi Murugan Kumar Susmita Bag Padmanaban Senthilvel Pandian Lavanya Rayapadi Swetha Anand Anbarasu Sudha Ramaiah 《Bioinformation》2013,9(8):432-439
Aromatic-aromatic hydrogen bonds are important in many areas of chemistry, biology and materials science. In this study we have
analyzed the roles played by the π-π interactions in interleukins (ILs) and tumor necrosis factor (TNF) proteins. Majority of π-π
interacting residues are conserved in ILs and TNF proteins. The accessible surface area calculations in these proteins reveal that
these interactions might be important in stabilizing the inner core regions of these proteins. In addition to π-π interactions, the
aromatic residues also form π-networks in ILs and TNF proteins. The results obtained in the present study indicate that π-π
interactions and π-π networks play important roles in the structural stability of ILs and TNF proteins. 相似文献
98.
Vinod K. Bisht Chandra P. Kuniyal Arvind K. Bhandari Bhagwati P. Nautiyal P. Prasad 《Physiology and Molecular Biology of Plants》2014,20(3):399-403
Observations on phenology of some representative trees, shrubs, under-shrubs and herbs in a subalpine forest of Uttarakhand, western Himalaya were recorded. With the commencement of favorable growth season in April, occurrence of leaf fall was indicatory growth phenomenon in Quercus semecarpifolia, Q. floribunda and Abies spectabilis. However, active vegetative growth in herbaceous species starts onward April and fruit maturation and seed dehiscence are completed from mid of September to October. In general, vegetative growth and reproductive stages in majority of the studied species seems to be dependent on adequate moisture content and also flowering and fruiting in subalpine plants correlate ambient temperature. 相似文献
99.
Significant quantitative differences in ethanol yields along with repression in acetic acid production were observed in Clostridium thermocellum strains SS21 and SS22 in the presence of H 2 , acetone and sodium azide. Exogenous H 2 addition (1.0 atm) increased the ethanol yields to 0.40 g/g and ethanol to acetate ratio to 5.75 in strain SS21 but was inhibitory in strain SS22. Addition of acetone reversed the inhibition caused by H 2 and increased the ethanol yields and ethanol to acetate ratio of strain SS22 up to 0.40 g/g and 7.9, respectively. Enhancement in ethanol yields up to 0.40 g/g and 0.41 g/g and ethanol to acetate ratio up to 3.63 and 8.1 were observed in the presence of 0.2 mM and 0.15 mM concentration of sodium azide by strains SS21 and SS22, respectively. 相似文献
100.
Efrapeptins are a group of microheterogeneous polypeptide antibiotics produced by the fungus Tolypocladium niveum, which are potent inhibitors of mitochondrial F1-ATPase. Efrapeptins contain an unusual 1,5-diazabicyclo[4:3:0]nonene (DBN) residue at the C-terminus. This study is driven by the hypothesis that the DBN residue could, in principle, arise by oxidative cyclization of a spermidine moiety. Electrospray ionization mass spectrometry of the peptide antibiotics 'elvapeptins' from T niveum establishes the presence of a C-terminal spermidine residue. Conversion of elvapeptins to efrapeptins by CuCl/pyridine demonstrates the transformation of the spermidine residue to the 1,5-diazabicyclo[4:3:0]nonene system by oxidative cyclization. 相似文献