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111.
Protein-protein interactions are driven by specific properties of the molecular surfaces. Cytochrome c, a small electron transfer protein, is involved in a number of biologically relevant interactions with macromolecular partners. Small molecules may interfere with such interactions by binding to the surface of cytochrome c. Here we investigated the possibility of weak intermolecular interactions between reduced cytochrome c and a library of 325 small molecules, using WaterLOGSY NMR spectroscopy. Specific binding was found for p-aminophenol. The solution structure of the p-aminophenol-cytochrome c adduct was determined using a combination of in silico tools and NMR-based restraints. The ligand interacts in a specific binding site on the protein surface through a combination of stacking and H-bond interactions. Small but meaningful rearrangements of the solvent-exposed side chains are observed upon ligand binding and contribute to the stabilization of the complex. 相似文献
112.
The G37R copper-zinc superoxide dismutase (SOD1) is one of the many mutant SOD1 proteins known to cause familial amyotrophic lateral sclerosis by an unknown mechanism. This particular mutation occurs in the beta barrel plug, a region proposed to be critical for the structural stability of the protein. The behavior of G37R asSOD1 was studied in solution where it was observed that, when the protein is fully metalated, its global structure, mobility, and stability are virtually indistinguishable from those of the nonmutated protein. By contrast, although the presence of the G37R mutation does not result in a substantial change of the overall structure of the metal-free apoprotein in solution, it does affect the key conformational features of the beta-barrel plug such that (i) apo G37R asSOD1 melts at a temperature approximately 10 degrees C lower than apo asSOD1, (ii) it aggregates more rapidly than apo asSOD1, and (iii) interaction with trifluoroethanol (TFE) can deform it into a structure with a much higher degree of alpha-helical content. The increased plasticity of the apo G37R asSOD1 mutant protein is likely responsible for its enhanced tendency to aggregate in concentrated solutions. These results suggest further that it is the metal-free apo forms of the mutant SOD1 protein that are the agents of its toxicity. 相似文献
113.
114.
Simone Guglielmetti Ivan Zanoni Silvia Balzaretti Matteo Miriani Valentina Taverniti Ivano De Noni Ilaria Presti Milda Stuknyte Alessio Scarafoni Stefania Arioli Stefania Iametti Francesco Bonomi Diego Mora Matti Karp Francesca Granucci 《Applied and environmental microbiology》2014,80(17):5170-5177
Bifidobacteria are Gram-positive inhabitants of the human gastrointestinal tract that have evolved close interaction with their host and especially with the host''s immune system. The molecular mechanisms underlying such interactions, however, are largely unidentified. In this study, we investigated the immunomodulatory potential of Bifidobacterium bifidum MIMBb75, a bacterium of human intestinal origin commercially used as a probiotic. Particularly, we focused our attention on TgaA, a protein expressed on the outer surface of MIMBb75''s cells and homologous to other known bacterial immunoactive proteins. TgaA is a peptidoglycan lytic enzyme containing two active domains: lytic murein transglycosylase (LT) and cysteine- and histidine-dependent amidohydrolase/peptidase (CHAP). We ran immunological experiments stimulating dendritic cells (DCs) with the B. bifidum MIMBb75 and TgaA, with the result that both the bacterium and the protein activated DCs and triggered interleukin-2 (IL-2) production. In addition, we observed that the heterologous expression of TgaA in Bifidobacterium longum transferred to the bacterium the ability to induce IL-2. Subsequently, immunological experiments performed using two purified recombinant proteins corresponding to the single domains LT and CHAP demonstrated that the CHAP domain is the immune-reactive region of TgaA. Finally, we also showed that TgaA-dependent activation of DCs requires the protein CD14, marginally involves TRIF, and is independent of Toll-like receptor 4 (TLR4) and MyD88. In conclusion, our study suggests that the bacterial CHAP domain is a novel microbe-associated molecular pattern actively participating in the cross talk mechanisms between bifidobacteria and the host''s immune system. 相似文献
115.
Daniele Cespi Fabrizio Passarini Luca Ciacci Ivano Vassura Valentina Castellani Elena Collina Andrea Piazzalunga Luciano Morselli 《The International Journal of Life Cycle Assessment》2014,19(1):89-99
Purpose
Biomass provides an attractive solution for residential heating systems based on renewable fuels, even though biomass-based domestic heating systems are recognized as significant particulate matter emitters; thus, a life cycle assessment (LCA) approach was used in the study to compare two different appliances: a wood stove and a pellet stove, both modeled according to the best available technologies definition.Methods
System boundaries of each scenario refer to a cradle-to-grave approach, including production, use and disposal of the heating appliance, as well as the preparation of biomass feedstock. The assessment of environmental impacts was performed assuming 1 MJ of thermal energy as the reference flow, considering the categories of particulate matter formation, human toxicity, climate change, and fossil fuel depletion, according to the ReCiPe 1.07 method. Finally, the comparison was extended to certain innovative heating systems in order to qualitatively evaluate potential improvements in residential heating performances.Results and discussion
The results show that the wood stove reaches the highest scores in the categories of particulate matter formation and negative effects for human toxicity, as a consequence of the stove’s lower combustion efficiency, which would lead to a preference for the pellet stove. However, when climate change affecting human health and the ecosystem, and fossil depletion are considered, the choice appears more uncertain due to the energy consumption from the pelletizing step. Alternative technologies (e.g., solar panels in combination with a gas boiler) show better scores related to fine particles emission reduction, even if a worsening in other categories is observed. The results were validated by a sensitivity analysis.Conclusions
The study suggests that a LCA approach can support the choice of the best domestic heating system, helping to promote policy initiatives on a sound basis and to understand which are the main key levers to act for reducing the total environmental burdens of biomass-based heating appliances. 相似文献116.
de Filippis I de Lemos AP Hostetler JB Wollenberg K Sacchi CT Dunning Hotopp JC Harrison LH Bash MC Prevots DR 《PloS one》2012,7(3):e33016
Background
Neisseria meningitidis serogroup B has been predominant in Brazil, but no broadly effective vaccine is available to prevent endemic meningococcal disease. To understand genetic diversity among serogroup B strains in Brazil, we selected a nationally representative sample of clinical disease isolates from 2004, and a temporally representative sample for the state of São Paulo (1988–2006) for study (n = 372).Methods
We performed multi-locus sequence typing (MLST) and sequence analysis of five outer membrane protein (OMP) genes, including novel vaccine targets fHbp and nadA.Results
In 2004, strain B:4:P1.15,19 clonal complex ST-32/ET-5 (cc32) predominated throughout Brazil; regional variation in MLST sequence type (ST), fetA, and porB was significant but diversity was limited for nadA and fHbp. Between 1988 and 1996, the São Paulo isolates shifted from clonal complex ST-41/44/Lineage 3 (cc41/44) to cc32. OMP variation was associated with but not predicted by cc or ST. Overall, fHbp variant 1/subfamily B was present in 80% of isolates and showed little diversity. The majority of nadA were similar to reference allele 1.Conclusions
A predominant serogroup B lineage has circulated in Brazil for over a decade with significant regional and temporal diversity in ST, fetA, and porB, but not in nadA and fHbp. 相似文献117.
Eberini I Guerini Rocco A Ientile AR Baptista AM Gianazza E Tomaselli S Molinari H Ragona L 《Proteins》2008,71(4):1889-1898
The correlation between protein motions and function is a central problem in protein science. Several studies have demonstrated that ligand binding and protein dynamics are strongly correlated in intracellular lipid binding proteins (iLBPs), in which the high degree of flexibility, principally occurring at the level of helix-II, CD, and EF loops (the so-called portal area), is significantly reduced upon ligand binding. We have recently investigated by NMR the dynamic properties of a member of the iLBP family, chicken liver bile acid binding protein (cL-BABP), in its apo and holo form, as a complex with two bile salts molecules. Binding was found to be regulated by a dynamic process and a conformational rearrangement was associated with this event. We report here the results of molecular dynamics (MD) simulations performed on apo and holo cL-BABP with the aim of further characterizing the protein regions involved in motion propagation and of evaluating the main molecular interactions stabilizing bound ligands. Upon binding, the root mean square fluctuation values substantially decrease for CD and EF loops while increase for the helix-loop-helix region, thus indicating that the portal area is the region mostly affected by complex formation. These results nicely correlate with backbone dynamics data derived from NMR experiments. Essential dynamics analysis of the MD trajectories indicates that the major concerted motions involve the three contiguous structural elements of the portal area, which however are dynamically coupled in different ways whether in the presence or in the absence of the ligands. Motions of the EF loop and of the helical region are part of the essential space of both apo and holo-BABP and sample a much wider conformational space in the apo form. Together with NMR results, these data support the view that, in the apo protein, the flexible EF loop visits many conformational states including those typical of the holo state and that the ligand acts stabilizing one of these pre-existing conformations. The present results, in agreement with data reported for other iLBPs, sharpen our knowledge on the binding mechanism for this protein family. 相似文献
118.
The major limitation of nuclear magnetic resonance spectroscopy arises from the increase of nuclear transverse relaxation rates with increasing molecular mass. This causes reduction in spectral resolution and coherence transfer efficiency. The use of 2H-labeling to eliminate 1H-mediated relaxation pathways and the constructive use of cross correlation effects (TROSY, CRINEPT) alleviate the phenomenon. An alternative approach is to use direct detection of heteronuclei. Specifically designed 13C direct detection experiments can complement the set of 1H-based NMR experiments commonly used for structure determination providing an additional source of information less affected by the detrimental transverse relaxation effect. We applied this novel methodology to the study of the CutA1 protein (12.3 kDa) from E. coli that forms a homotrimer in solution with a total molecular mass of 37 kDa. In this work we demonstrate that the information available from 13C direct detection experiments makes it possible to completely assign the NMR resonances of the backbone of this 37 kDa trimeric protein without the need of deuteration. The structural and dynamical knowledge obtained for this system may contribute to understand its biological role. 相似文献
119.
In high-throughput genome-level protein investigation efforts, such as Structural Genomics, the systematic experimental characterization of metal-binding properties (i.e., the investigation of the metalloproteome) is not always pursued and remains far from trivial. In the present work, we have applied a bioinformatic approach to investigate the occurrence of (putative) copper-binding proteins in 57 different organisms spanning the entire tree of life. We found that the size of the copper proteome is generally less than 1% of the total proteome of an organism, in both eukaryotes and prokaryotes. The occurrence of copper-binding proteins is relatively scarce when compared to that of zinc-binding proteins and of non-heme iron proteins. This may be due to both poorer bioavailability (in particular with respect to iron in the ancient world) and the complexity of copper chemistry and the risks associated with it, which may have adversely affected natural selection of copper-binding proteins. The present analysis shows that there is a strong relationship between the metal coordination sphere and protein function. A network involving proteins having roles in both copper transport and respiration was identified, parts or all of which are detected in the majority of the organisms examined. 相似文献
120.
Role of the GM1 ganglioside oligosaccharide portion in the TrkA‐dependent neurite sprouting in neuroblastoma cells
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