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61.
The preferred conformations of the glycerol region of a phospholipid have been explored using replica exchange molecular dynamics
(MD) simulations and compared with the results of standard MD approaches and with experiment. We found that due to isomerization
rates in key torsions that are slow on the timescale of atomistic MD simulations, standard MD is not able to produce accurate
equilibrium conformer distributions from reasonable trajectory lengths (e.g., on the 100 ns) timescale. Replica exchange MD,
however, results in quite efficient sampling due to the rapid increase in isomerization rate with temperature. The equilibrium
distributions obtained from replica exchange MD have been compared with the results of experimental nuclear magnetic resonance
observations. This comparison suggests that the sampling approach demonstrated here is a valuable tool that can be used in
evaluating force fields for molecular simulation of lipids. 相似文献
62.
T Akerström J Crona A Delgado Verdugo LF Starker K Cupisti HS Willenberg WT Knoefel W Saeger A Feller J Ip P Soon M Anlauf PF Alesina KW Schmid M Decaussin P Levillain B Wängberg JL Peix B Robinson J Zedenius M Bäckdahl S Caramuta KA Iwen J Botling P Stålberg JL Kraimps H Dralle P Hellman S Sidhu G Westin H Lehnert MK Walz G Akerström T Carling M Choi RP Lifton P Björklund 《PloS one》2012,7(7):e41926
Background
Aldosterone producing lesions are a common cause of hypertension, but genetic alterations for tumorigenesis have been unclear. Recently, either of two recurrent somatic missense mutations (G151R or L168R) was found in the potassium channel KCNJ5 gene in aldosterone producing adenomas. These mutations alter the channel selectivity filter and result in Na+ conductance and cell depolarization, stimulating aldosterone production and cell proliferation. Because a similar mutation occurs in a Mendelian form of primary aldosteronism, these mutations appear to be sufficient for cell proliferation and aldosterone production. The prevalence and spectrum of KCNJ5 mutations in different entities of adrenocortical lesions remain to be defined.Materials and Methods
The coding region and flanking intronic segments of KCNJ5 were subjected to Sanger DNA sequencing in 351 aldosterone producing lesions, from patients with primary aldosteronism and 130 other adrenocortical lesions. The specimens had been collected from 10 different worldwide referral centers.Results
G151R or L168R somatic mutations were identified in 47% of aldosterone producing adenomas, each with similar frequency. A previously unreported somatic mutation near the selectivity filter, E145Q, was observed twice. Somatic G151R or L168R mutations were also found in 40% of aldosterone producing adenomas associated with marked hyperplasia, but not in specimens with merely unilateral hyperplasia. Mutations were absent in 130 non-aldosterone secreting lesions. KCNJ5 mutations were overrepresented in aldosterone producing adenomas from female compared to male patients (63 vs. 24%). Males with KCNJ5 mutations were significantly younger than those without (45 vs. 54, respectively; p<0.005) and their APAs with KCNJ5 mutations were larger than those without (27.1 mm vs. 17.1 mm; p<0.005).Discussion
Either of two somatic KCNJ5 mutations are highly prevalent and specific for aldosterone producing lesions. These findings provide new insight into the pathogenesis of primary aldosteronism. 相似文献63.
Bauvois C Jacquamet L Huston AL Borel F Feller G Ferrer JL 《The Journal of biological chemistry》2008,283(34):23315-23325
The crystal structure of a cold-active aminopeptidase (ColAP) from Colwellia psychrerythraea strain 34H has been determined, extending the number of crystal structures of the M1 metallopeptidase family to four among the 436 members currently identified. In agreement with their sequence similarity, the overall structure of ColAP displayed a high correspondence with leukotriene A4 hydrolase (LTA4H), a human bifunctional enzyme that converts leukotriene A4 (LTA4) in the potent chemoattractant leukotriene B4. Indeed, both enzymes are composed of three domains, an N-terminal saddle-like domain, a catalytic thermolysin-like domain, and a less conserved C-terminal alpha-helical flat spiral domain. Together, these domains form a deep cavity harboring the zinc binding site formed by residues included in the conserved HEXXHX(18)H motif. A detailed structural comparison of these enzymes revealed several plausible determinants of ColAP cold adaptation. The main differences involve specific amino acid substitutions, loop content and solvent exposure, complexity and distribution of ion pairs, and differential domain flexibilities. Such elements may act synergistically to allow conformational flexibility needed for an efficient catalysis in cold environments. Furthermore, the region of ColAP corresponding to the aminopeptidase active site of LTA4H is much more conserved than the suggested LTA4 substrate binding region. This observation supports the hypothesis that this region of the LTA4H active site has evolved in order to fit the lipidic substrate. 相似文献
64.
The relationships between structure, activity, stability and flexibility of a cold-adapted aminopeptidase produced by a psychrophilic marine bacterium have been investigated in comparison with a mesophilic structural and functional human homolog. Differential scanning calorimetry, fluorescence monitoring of thermal- and guanidine hydrochloride-induced unfolding and fluorescence quenching were used to show that the cold-adapted enzyme is characterized by a high activity at low temperatures, a low structural stability versus thermal and chemical denaturants and a greater structural permeability to a quenching agent relative to the mesophilic homolog. These findings support the hypothesis that cold-adapted enzymes maintain their activity at low temperatures as a result of increased global or local structural flexibility, which results in low stability. Analysis of the thermodynamic parameters of irreversible thermal unfolding suggests that entropy-driven factors are responsible for the fast unfolding rate of the cold-adapted aminopeptidase. A reduced number of proline residues, a lower degree of hydrophobic residue burial and a decreased surface accessibility of charged residues may be responsible for this effect. On the other hand, the reduction in enthalpy-driven interactions is the primary determinant of the weak conformational stability. 相似文献
65.
Manlay Raphaël J. Masse Dominique Chevallier Tiphaine Russell-Smith Anthony Friot Dominique Feller Christian 《Plant and Soil》2004,259(1-2):123-136
Potassium (K), calcium (Ca), iron (Fe) and aluminium (Al) release from Norway spruce (Picea abies Karsten), Scots pine (Pinus sylvestris L.) and silver birch (Betula pendula Roth.) logging residues (fine roots, foliage and small branches) were studied by means of litterbags over a period of three years in clear-cut area and adjacent uncut Norway spruce dominated mixed boreal forest in eastern Finland (63°51′ N, 28°58′ E, 220 m a.s.l) to determine the amounts and rates of release for these elements and to evaluate whether clear-cutting accelerates mineralization. Almost all K was released from logging residues already during the first year. Calcium was released from foliage and roots but accumulated in branches. Most of the roots Fe and Al content were released during three years while the absolute amounts of Fe and Al in branches and foliage generally increased with decomposition. The results indicate that mineralization is slightly accelerated as a result of clear-cutting since K from foliage and branches of all studied tree species and Ca from pine and spruce roots was released significantly faster at the clear-cut plot than at the forest plot. In three years the initial K pool in the logging residues declined by 90%, Ca by 8%, Fe by 55% and Al by 61% in the clear-cut area. These results indicate that Ca is retained a long time; but Fe, Al and in particular, K are soon released from logging residues. Fine roots of the logged trees release large amounts of Fe and Al and can significantly affect Fe and Al fluxes. 相似文献
66.
Cold-Adapted β-Galactosidase from the Antarctic Psychrophile Pseudoalteromonas haloplanktis 下载免费PDF全文
A. Hoyoux I. Jennes P. Dubois S. Genicot F. Dubail J. M. Franois E. Baise G. Feller C. Gerday 《Applied microbiology》2001,67(4):1529-1535
The β-galactosidase from the Antarctic gram-negative bacterium Pseudoalteromonas haloplanktis TAE 79 was purified to homogeneity. The nucleotide sequence and the NH2-terminal amino acid sequence of the purified enzyme indicate that the β-galactosidase subunit is composed of 1,038 amino acids with a calculated Mr of 118,068. This β-galactosidase shares structural properties with Escherichia coli β-galactosidase (comparable subunit mass, 51% amino sequence identity, conservation of amino acid residues involved in catalysis, similar optimal pH value, and requirement for divalent metal ions) but is characterized by a higher catalytic efficiency on synthetic and natural substrates and by a shift of apparent optimum activity toward low temperatures and lower thermal stability. The enzyme also differs by a higher pI (7.8) and by specific thermodynamic activation parameters. P. haloplanktis β-galactosidase was expressed in E. coli, and the recombinant enzyme displays properties identical to those of the wild-type enzyme. Heat-induced unfolding monitored by intrinsic fluorescence spectroscopy showed lower melting point values for both P. haloplanktis wild-type and recombinant β-galactosidase compared to the mesophilic enzyme. Assays of lactose hydrolysis in milk demonstrate that P. haloplanktis β-galactosidase can outperform the current commercial β-galactosidase from Kluyveromyces marxianus var. lactis, suggesting that the cold-adapted β-galactosidase could be used to hydrolyze lactose in dairy products processed in refrigerated plants. 相似文献
67.
Nitrogen vs. phosphorus limitation across an ecotonal gradient in a mangrove forest 总被引:10,自引:1,他引:9
Mangrove forests are characterized by distinctive tree-height gradientsthat reflect complex spatial, within-stand differences in environmentalfactors,including nutrient dynamics, salinity, and tidal inundation, across narrowgradients. To determine patterns of nutrient limitation and the effects ofnutrient availability on plant growth and within-stand nutrient dynamics, weused a factorial experiment with three nutrient treatment levels (control, N,P)and three zones along a tree-height gradient (fringe, transition, dwarf) onoffshore islands in Belize. Transects were laid out perpendicular to theshoreline across a mangrove forest from a fringe stand along the seaward edge,through a stand of intermediate height, into a dwarf stand in the interior ofthe island. At three sites, three trees were fertilized per zone for 2yr. Although there was spatial variability in response, growth byR. mangle was generally nitrogen (N) -limited in thefringe zone;phosphorus (P) -limited in the dwarf zone; and, N- and/or P-limited in thetransition zone. Phosphorus-resorption efficiency decreased in all three zones,and N-resorption efficiency increased in the dwarf zone in response to Penrichment. The addition of N had no effect on either P or N resorptionefficiencies. Belowground decomposition was increased by P enrichment in allzones, whereas N enrichment had no effect. This study demonstrated thatessential nutrients are not uniformly distributed within mangrove ecosystems;that soil fertility can switch from conditions of N to P limitation acrossnarrow ecotonal gradients; and, that not all ecological processes respondsimilarly to, or are limited by, the same nutrient. 相似文献
68.
69.
S Cunningham-Rundles W F Feller C Cunningham-Rundles B Dupont H Wanebo R O'Reilly R A Good 《Cellular immunology》1976,25(2):322-327
The cell-mediated immune responses of 110 women with benign or malignant breast disease were tested in in vitro lymphocyte transformation assay with an antigen preparation made from RIII mouse milk containing mammary tumor virus. About 50% of patients responded positively to the milk preparation. In contrast, 25% of normal women or women with other gynecological malignancies responded positively to the antigen (P = 0.015). The data demonstrate a similar response pattern among women with malignant or benign breast disease. In addition, a subpopulation of normal women with positive response to this antigen is clearly defined. 相似文献
70.