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61.
Parthasarathy K Lin X Tan SM Law SK Torres J 《Protein science : a publication of the Protein Society》2008,17(5):930-938
Integrins are alpha/beta heterodimers, but recent in vitro and in vivo experiments also suggest an ability to associate through their transmembrane domains to form homomeric interactions. While the results of some in vitro experiments are consistent with an interaction mediated by a GxxxG-like motif, homo-oligomers observed after in vivo cross-linking are consistent with an almost opposite helix-helix interface. We have shown recently that both models of interaction are compatible with evolutionary conservation data, and we predicted that the alpha-helices in both models would have a similar rotational orientation. Herein, we have tested our prediction using in vitro asparagine scan of five consecutive residues along the GxxxG-like motif of the transmembrane domain of alpha and beta integrins, alphaM and beta2. We show that Asn-mediated dimerization occurs twice for every turn of the helix, consistent with two almost opposite forms of interaction as suggested previously for alphaIIb and beta3 transmembrane domains. The orientational parameters helix tilt and rotational orientation of each of these two Asn-stabilized dimers were measured by site-specific infrared dichroism (SSID) in model lipid bilayers and were found to be consistent with our predicted computational models. Our results highlight an intrinsic tendency for integrin transmembrane alpha-helices to form two opposite types of homomeric interaction in addition to their heteromeric interactions and suggest that integrins may form complex and specific networks at the transmembrane domain during function. 相似文献
62.
Metyrapone, a specific inhibitor of 11beta-hydroxylase inhibits glucocorticoid production and it is used in the diagnosis/treatment of hypercortisolism and also to test the functional integrity of hypothalamo-pituitary-adrenal axis. To assess the impact of glucocorticoid deficiency, this drug is preferred over adrenalectomy, which eliminates all the hormonal secretions of the adrenal cortex and medulla. However, whether metyrapone has any direct effect on the extra-adrenocortical cellular or tissue functions remains to be resolved. Our previous study showed a depressed testicular Leydig cell testosterone production in rats treated with metyrapone. Therefore, the present study was designed to examine the possible direct effect of metyrapone on testicular Leydig cell steroidogenesis in vitro. Leydig cell viability and the reactive oxygen species (ROS) concentration were not altered by any of the concentration of metyrapone tested. The efficacy of Leydig cell testosterone production under basal as well as LH-stimulated condition was not altered by metyrapone treatment. Further, Leydig cellular (14)C-glucose oxidation, the activity and mRNA levels of cytochrome side chain cleavage (P(450)scc), 3beta- and 17beta-hydroxysteroid dehydrogenase (3beta-HSD and 17beta-HSD) were not altered in metyrapone-treated cells. Therefore, it is concluded from the present study that metyrapone has no direct effect on Leydig cell testosterone production and, therefore, changes recorded in the in vivo studies are exclusively due to corticosterone deficiency. 相似文献
63.
N-Nitrosodiethylamine (DEN) is a notorious carcinogen, present in many environmental factors. DEN induces oxidative stress
and cellular injury due to enhanced generation of reactive oxygen species; free radical scavengers protect the membranes from
DEN-induced damage. The present study was designed to evaluate the protective effect of bacoside A (the active principle isolated
from Bacopa monniera Linn.) on carcinogen-induced damage in rat liver. Adult male albino rats were pretreated with 15 mg/kg body weight/day of
bacoside A orally (for 14 days) and then intoxicated with single necrogenic dose of N-nitrosodiethylamine (200 mg/kg bodyweight, intraperitonially) and maintained for 7 days. The liver weight, lipid peroxidation
(LPO), and activity of serum marker enzymes (aspartate transaminases, alanine transaminases, lactate dehydrogenase, alkaline
phosphatase, and γ-glutamyl transpeptidase) were markedly increased in carcinogen-administered rats, whereas the activities
of marker enzymes were near normal in bacoside A-pretreated rats. Activities of antioxidant enzymes (superoxide dismutase,
catalase, glutathione peroxidase, glutathione reductase, glutatione-S-transferase, and reduced glutathione) in liver also decreased in carcinogen-administered rats, which were significantly elevated
in bacoside A-pretreated rats. It is concluded that pretreatment of bacoside A prevents the elevation of LPO and activity
of serum marker enzymes and maintains the antioxidant system and thus protects the rats from DEN-induced hepatotoxicity. 相似文献
64.
Species richness and density of understory plants were investigated in eight 1 ha plots, distributed one each in undisturbed
and disturbed tropical evergreen, semi-evergreen, deciduous and littoral forests of Little Andaman island, India, which falls
under one of the eight hottest hotspots of Biodiversity in the world viz. the Indo-Burma. One hundred 1 m−2 quadrats were established in each 1 ha plot, in which all the understory plants (that include herbs, undershrubs, shrubs
and herbaceous climbers) were enumerated. The total density of understory plants was 6,812 individuals (851 ha−1) and species richness was 108 species, representing 104 genera and 50 families. Across the four forest types and eight study
plots, the species richness ranged from 10 to 39 species ha−1. All the disturbed sites harbored greater number of species than their undisturbed counterparts. Herbs dominated by species
(63%) and density (4,259 individuals). The grass Eragrostis tenella (1,860 individuals; IVI 40), the invasive climber Mikania cordata (803; IVI 20) and the shrub Anaxagorea luzonensis (481; IVI 17.5) were the most abundant species. Poaceae, Asteraceae, Acanthaceae, Orchidaceae and Euphorbiaceae constituted
the species-rich families represented by 6 species each. The species-area curves attained an asymptote at 0.8 ha level except
in sites DD and DL, indicating 1 ha plot is not sufficient to capture all the understory species in disturbed forests. The
alien weeds formed about one-fourth of the species richness (31 species; 28%) and density (1,926 individuals; 28.3%) in the
study sites, indicating the extent of weed invasion and the attention required for effective conservation of the native biodiversity
of the fragile island forest ecosystem. 相似文献
65.
Hong C. Shen Fa-Xiang Ding Sheo B. Singh Gopalakrishnan Parthasarathy Stephen M. Soisson Sookhee N. Ha Xun Chen Srinivas Kodali Jun Wang Karen Dorso James R. Tata Milton L. Hammond Malcolm MacCoss Steven L. Colletti 《Bioorganic & medicinal chemistry letters》2009,19(6):1623-1627
Platensimycin (1) displays antibacterial activity due to its inhibition of the elongation condensing enzyme (FabF), a novel mode of action that could potentially lead to a breakthrough in developing a new generation of antibiotics. The medicinal chemistry efforts were focused on the modification of the enone moiety of platensimycin and several analogs showed significant activity against FabF and possess antibacterial activity. 相似文献
66.
Konstantin Pervushin Edward Tan Krupakar Parthasarathy Xin Lin Feng Li Jiang Dejie Yu Ardcharaporn Vararattanavech Tuck Wah Soong Ding Xiang Liu Jaume Torres 《PLoS pathogens》2009,5(7)
The envelope (E) protein from coronaviruses is a small polypeptide that contains at least one α-helical transmembrane domain. Absence, or inactivation, of E protein results in attenuated viruses, due to alterations in either virion morphology or tropism. Apart from its morphogenetic properties, protein E has been reported to have membrane permeabilizing activity. Further, the drug hexamethylene amiloride (HMA), but not amiloride, inhibited in vitro ion channel activity of some synthetic coronavirus E proteins, and also viral replication. We have previously shown for the coronavirus species responsible for severe acute respiratory syndrome (SARS-CoV) that the transmembrane domain of E protein (ETM) forms pentameric α-helical bundles that are likely responsible for the observed channel activity. Herein, using solution NMR in dodecylphosphatidylcholine micelles and energy minimization, we have obtained a model of this channel which features regular α-helices that form a pentameric left-handed parallel bundle. The drug HMA was found to bind inside the lumen of the channel, at both the C-terminal and the N-terminal openings, and, in contrast to amiloride, induced additional chemical shifts in ETM. Full length SARS-CoV E displayed channel activity when transiently expressed in human embryonic kidney 293 (HEK-293) cells in a whole-cell patch clamp set-up. This activity was significantly reduced by hexamethylene amiloride (HMA), but not by amiloride. The channel structure presented herein provides a possible rationale for inhibition, and a platform for future structure-based drug design of this potential pharmacological target. 相似文献
67.
68.
Parthasarathy S Altuve A Terzyan S Zhang X Kuczera K Rivera M Benson DR 《Biochemistry》2011,50(24):5544-5554
Mammalian type B (mitochondrial) b(5) cytochromes exhibit greater amino acid sequence diversity than their type A (microsomal) counterparts, as exemplified by the type B proteins from human (hCYB5B) and rat (rCYB5B). The comparison of X-ray crystal structures of hCYB5B and rCYB5B reported herein reveals a striking difference in packing involving the five-strand β-sheet, which can be attributed to fully buried residue 21 in strand β4. The greater bulk of Leu21 in hCYB5B in comparison to that of Thr21 in rCYB5B results in a substantial displacement of the first two residues in β5, and consequent loss of two of the three hydrogen bonds between β5 and β4. Hydrogen bonding between the residues is instead mediated by two well-ordered, fully buried water molecules. In a 10 ns molecular dynamics simulation, one of the buried water molecules in the hCYB5B structure exchanged readily with solvent via intermediates having three water molecules sandwiched between β4 and β5. When the buried water molecules were removed prior to a second 10 ns simulation, β4 and β5 formed persistent hydrogen bonds identical to those in rCYB5B, but the Leu21 side chain was forced to adopt a rarely observed conformation. Despite the apparently greater ease of access of water to the interior of hCYB5B than of rCYB5B suggested by these observations, the two proteins exhibit virtually identical stability, dynamic, and redox properties. The results provide new insight into the factors stabilizing the cytochrome b(5) fold. 相似文献
69.
Jed P. Sparks Subhash Chandra Louis A. Derry Mandayam V. Parthasarathy Carole S. Daugherty Rory Griffin 《Biogeochemistry》2011,104(1-3):237-249
Silicon transport and incorporation into plant tissue is important to both plant physiological function and to the influence plants have on ecosystem silica cycling. However, the mechanisms controlling this transport have only begun to be explored. In this study, we used secondary ion mass spectrometry (SIMS) to image concentrations of Si in root and shoot tissues of annual blue grass (Poa annua L.) and orchard grass (Dactylis glomerata L.) with the goal of identifying control points in the plant silica uptake pathway. In addition, we used SIMS to describe the distributions of germanium (Ge); the element used to trace Si in biogeochemical studies. Within root tissue, Si and Ge were localized in the suberized thick-walled region of endodermal cells, i.e. the proximal side of endodermal cells which is in close association to the casparian strip. In leaves, Si was present in the cell walls, but Ge was barely detectable. The selective localization of Si and Ge in the proximal side of endodermal cell walls of roots suggests transport control is exerted upon Si and Ge by the plant. The absence of Si in most root cell walls and its presence in the cell walls of leaves (in areas outside of the transpiration terminus) suggests modifications in the chemical form of Si to a form that favors Si complexation in the cell walls of leaf tissue. The low abundance of Ge in leaf tissue is consistent with previous studies that suggest preferential transport of Si relative to Ge. 相似文献
70.
Apeksha Sahu Satwant Kumar Sreelakshmi K Sreenivasamurthy Lakshmi Dhevi N Selvan Anil K Madugundu Soujanya D Yelamanchi Vinuth N Puttamallesh Gourav Dey Abhijith K Anil Anand Srinivasan Kanchan K Mukherjee Harsha Gowda Parthasarathy Satishchandra Anita Mahadevan Akhilesh Pandey Thottethodi Subrahmanya Keshava Prasad Susarla Krishna Shankar 《Clinical proteomics》2014,11(1)