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661.
Jaume Bonet Gianluigi Caltabiano Abdul Kareem Khan Michael A. Johnston Carles Corbí lex Gmez Xavier Rovira Joan Teyra Jordi Vill‐Freixa 《Proteins》2006,63(1):65-77
Finding why protein–protein interactions (PPIs) are so specific can provide a valuable tool in a variety of fields. Statistical surveys of so‐called transient complexes (like those relevant for signal transduction mechanisms) have shown a tendency of polar residues to participate in the interaction region. Following this scheme, residues in the unbound partners have to compete between interacting with water or interacting with other residues of the protein. On the other hand, several works have shown that the notion of active site electrostatic preorganization can be used to interpret the high efficiency in enzyme reactions. This preorganization can be related to the instability of the residues important for catalysis. In some enzymes, in addition, conformational changes upon binding to other proteins lead to an increase in the activity of the enzymatic partner. In this article the linear response approximation version of the semimacroscopic protein dipoles Langevin dipoles (PDLD/S‐LRA) model is used to evaluate the stability of several residues in two phosphate hydrolysis enzymes upon complexation with their activating partners. In particular, the residues relevant for PPI and for phosphate hydrolysis in the CDK2/Cyclin A and Ras/GAP complexes are analyzed. We find that the evaluation of the stability of residues in these systems can be used to identify not only active site regions but it can also be used as a guide to locate “hot spots” for PPIs. We also show that conformational changes play a major role in positioning interfacing residues in a proper “energetic” orientation, ready to interact with the residues in the partner protein surface. Thus, we extend the preorganization theory to PPIs, extrapolating the results we obtained from the above‐mentioned complexes to a more general case. We conclude that the correlation between stability of a residue in the surface and the likelihood that it participates in the interaction can be a general fact for transient PPIs. Proteins 2006. © 2005 Wiley‐Liss, Inc. 相似文献
662.
Luis Franco-Serrano Mario Huerta Sergio Hernández Juan Cedano JosepAntoni Perez-Pons Jaume Piñol Angel Mozo-Villarias Isaac Amela Enrique Querol 《The protein journal》2018,37(5):444-453
Multifunctionality or multitasking is the capability of some proteins to execute two or more biochemical functions. The objective of this work is to explore the relationship between multifunctional proteins, human diseases and drug targeting. The analysis of the proportion of multitasking proteins from the MultitaskProtDB-II database shows that 78% of the proteins analyzed are involved in human diseases. This percentage is much higher than the 17.9% found in human proteins in general. A similar analysis using drug target databases shows that 48% of these analyzed human multitasking proteins are targets of current drugs, while only 9.8% of the human proteins present in UniProt are specified as drug targets. In almost 50% of these proteins, both the canonical and moonlighting functions are related to the molecular basis of the disease. A procedure to identify multifunctional proteins from disease databases and a method to structurally map the canonical and moonlighting functions of the protein have also been proposed here. Both of the previous percentages suggest that multitasking is not a rare phenomenon in proteins causing human diseases, and that their detailed study might explain some collateral drug effects. 相似文献
663.
Jaume Pellicer FLS Sònia Garcia Joan Vallès Katsuhiko Kondo FLS Teresa Garnatje 《Botanical journal of the Linnean Society. Linnean Society of London》2013,171(4):655-666
Fluorescence in situ hybridization (FISH) with 35S and 5S rDNA probes was used to characterize cytogenetically representatives of Artemisia subgenus Dracunculus and allied species and to explore their evolution following polyploidization. At the diploid level two rDNA loci were observed in most species belonging to the A. dracunculus complex, a pattern considered to be the ancestral state for diploid Artemisia. In contrast, representative species from the Eurasian grade which belong to the other major lineage of the subgenus had more heterogeneous rDNA profiles, with three to five loci at the diploid level. Divergent patterns of locus evolution were also detected in polyploids, with the number and distribution of rDNA loci broadly fitting the two main diversification lineages in the subgenus. In the polyploid complex of A. dracunculus, the number of rDNA loci was almost proportional to ploidy, although monoploid genome size was shown to decrease with increasing ploidy. However, in polyploids from the Eurasian grade we found a remarkable reduction in the number of rDNA sites, suggesting that these species might have experienced either a complete loss of loci or a significant reduction in the number of repeats following polyploid formation. © 2013 The Linnean Society of London, Biological Journal of the Linnean Society, 2013 , 171 , 655–666. 相似文献
664.
Jeroni Galmés Iker Aranjuelo Hipólito Medrano Jaume Flexas 《Photosynthesis research》2013,117(1-3):73-90
The main objective of the present review is to provide a compilation of published data of the effects of several climatic conditions on Rubisco, particularly its activity, state of activation, and concentration, and its influence on leaf gas exchange and photosynthesis. The environmental conditions analyzed include drought, salinity, heavy metals, growth temperature, and elevated [O3], [CO2], and ultraviolet-B irradiance. The results show conclusive evidence for a major negative effect on activity of Rubisco with increasing intensity of a range of abiotic stress factors. This decrease in the activity of Rubisco is associated with down-regulation of the activation state of the enzyme (e.g., by de-carbamylation and/or binding of inhibitory sugar phosphates) in response to drought or high temperature. On the contrary, the negative effects of low temperature, heavy metal stress (cadmium), ozone, and UV-B stress on Rubisco activity are associated with changes in the concentration of Rubisco. Notably, in response to all environmental factors, the regulation of in vivo CO2 assimilation rate was related to Rubisco in vitro parameters, either concentration and/or carboxylation, depending on the particular stress. The importance of the loss of Rubisco activity and its repercussion on plant photosynthesis are discussed in the context of climate change. It is suggested that decreased Rubisco activity will be a major effect induced by climate change, which will need to be considered in any prediction model on plant productivity in the near future. 相似文献
665.
Alejandro Marín-Menéndez Azucena Bardají Flor E. Martínez-Espinosa Camila B?tto-Menezes Marcus V. Lacerda Jon Ortiz Pau Cisteró Mireia Piqueras Ingrid Felger Ivo Müeller Jaume Ordi Hernando del Portillo Clara Menéndez Mats Wahlgren Alfredo Mayor 《PLoS neglected tropical diseases》2013,7(4)
Background
Plasmodium vivax can potentially lead to life-threatening episodes but the mechanisms underlying severe disease remain poorly defined. Cytoadhesion of infected erythrocytes may contribute to P. vivax sequestration and organ injury although its physiological impact is still unknown. Here, we aimed to describe clinically-relevant cytoadhesive phenotypes of P. vivax isolates.Methodology/Principal findings
Rosetting and adhesion to CSA, CD36, ICAM1, placental and brain cryosections were determined in P. vivax peripheral isolates from 12 pregnant women, 24 non-pregnant women and 23 men from Manaus (Brazil). P. falciparum co-infection was excluded by PCR and P. vivax isolates were genotyped by assessing the size polymorphism of microsatellites ms2, ms20 and msp1F3 through capillary electrophoresis of PCR products. P. vivax monoinfection was confirmed by PCR in 59 isolates, with 50 (85%) of them being single-clone infections. One P. vivax haplotype was more frequently found among pregnant women (33%) than in non-pregnant women (0%) and men (4%; p = 0.010). Rosetting was observed in 64% of the isolates, adhesion to CSA in 15%, to ICAM1 in 12% and to placental cryosections in 9%, being similar among pregnant and non-pregnant groups. Intensity of rosetting was higher among anaemic individuals compared to non-anaemic (p = 0.010) and decreased with increasing haematocrit (p = 0.033) and haemoglobin levels (p = 0.015).Conclusions/Significance
P. vivax peripheral isolates from pregnant women do not exhibit a prominent adhesion to CSA, although other parasite phenotypes still unknown may increase the propagation of certain P. vivax clones observed among pregnant hosts. Rosetting is a frequent cytoadhesive phenotype in P. vivax infections that may contribute to the development of anaemia. 相似文献666.
Jonàs Juan-Mateu Lidia González-Quereda Maria José Rodríguez Edgard Verdura Kira Lázaro Cristina Jou Andrés Nascimento Cecilia Jiménez-Mallebrera Jaume Colomer Soledad Monges Fabiana Lubieniecki Maria Eugenia Foncuberta Samuel Ignacio Pascual-Pascual Jesús Molano Montserrat Baiget Pia Gallano 《PloS one》2013,8(3)
667.
668.
Roué G Pérez-Galán P López-Guerra M Villamor N Campo E Colomer D 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(3):1923-1930
In an attempt to circumvent the intrinsic resistance of mantle cell lymphoma (MCL) cells to apoptosis, we have analyzed their sensitivity to the extrinsic apoptotic signal triggered by TRAIL. We show here that TRAIL can trigger apoptosis in a majority of MCL cell lines and primary cultures, irrespective of receptor levels, Bcl-2 family members, or caspase regulator expression. MCL sensitivity to TRAIL was closely linked to the activity of the NF-kappaB p50 factor and to the consequent expression of cellular FLIP (c-FLIP), which accumulated into the TRAIL-dependent complex in resistant cells. c-FLIP transient knockdown overcame MCL resistance to TRAIL, while NF-kappaB inhibitors differentially modulated TRAIL cytotoxicity. Indeed, bortezomib increased TRAIL cytotoxic effects in sensitive cells, but led to the intracellular accumulation of c-FLIP, impeding full synergistic interaction. In contrast, the IkappaB kinase inhibitor BMS-345541 led to decreased c-FLIP expression and allowed all MCL samples to undergo TRAIL-mediated apoptosis. These results present the combination of TRAIL stimulation and IkappaB kinase inhibition as a new approach to MCL therapy. 相似文献
669.
Phytochemical studies on Galanthus nivalis of Bulgarian origin resulted in the isolation of five compounds: 11-O-(3'-hydroxybutanoyl)hamayne, 3,11-O-(3',3'-dihydroxybutanoyl)hamayne, 3-O-(2'-butenoyl)-11-O-(3'-hydroxybutanoyl)hamayne, 3,11,3'-O-(3',3',3'-trihydroxybutanoyl)hamayne, and 2-O-(3'-acetoxybutanoyl)lycorine, together with five known alkaloids: ungeremine, lycorine, tazettine, hamayne, and ismine. Their structures were determined by (1)H and (13)C NMR spectroscopy and two-dimensional (1)H-(1)H and (1)H-(13)C chemical shift correlation experiments. 相似文献
670.
In intensive horticultural crops, the choice of growing media and the adequate management of irrigation must ensure an optimal
trade-off between aeration and water supply to roots. The proportion of gas-filled pores and their composition can be strongly
affected by the water status and hence by irrigation. In this context, continuous measurement of gas exchange and water status
of the growing medium could bring out some insights into how irrigation events affect root activity and aeration in a time
scale of minutes to several hours. For this purpose, a measuring system was developed that measured the CO2 efflux rate from the entire substrate root system of pot plants while their shoots were kept outside, undisturbed. It was
able to monitor four plants at a time for several weeks at a rate of one measurement per plant every 10 min, thus tracing
the dynamics of CO2 efflux through a great many irrigation cycles. The results showed a marked pattern of CO2 efflux around each irrigation event, consisting mainly of a sharp, conspicuous peak followed by a depression until a threshold
in substrate water potential was reached. Analysis of these data suggests that the pattern is imposed mainly by the effects
of irrigation and water content on the mobility of gases in the growing medium. The peak can be explained by the CO2-enriched air being displaced by the water added to the growing medium in the pot, and the following depression can be the
result of the reduced mobility of gases when substrate water content is high. In spite of the great variation in the instantaneous
efflux rate of CO2, the integration of these CO2 values for the entire day provides a rather predictable value given the root biomass and does not seem to be affected by
the number of irrigation events that occur in a given day. 相似文献