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971.
Massimiliano Perduca Stefania Nicolis Barbara Mannucci Monica Galliano Hugo L. Monaco 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2018,1863(4):458-466
RBP4 (plasma retinol-binding protein) is the 21?kDa transporter of all-trans retinol that circulates in plasma as a moderately tight 1:1 molar complex of the vitamin with the protein. RBP4 is primarily synthesized in the liver but is also produced by adipose tissue and circulates bound to a larger protein, transthyretin, TTR, that serves to increase its molecular mass and thus avoid its elimination by glomerular filtration.This paper reports the high resolution three-dimensional structures of human RBP4 naturally lacking bound retinol purified from plasma, urine and amniotic fluid. In all these crystals we found a fatty acid molecule bound in the hydrophobic ligand-binding site, a result confirmed by mass spectrometry measurements.In addition we also report the 1.5?Å resolution structures of human holo-RBP4 and of the protein saturated with palmitic and lauric acid and discuss the interaction of the fatty acids and retinol with the protein. 相似文献
972.
Veyron-Churlet R Bigot S Guerrini O Verdoux S Malaga W Daffé M Zerbib D 《Journal of molecular biology》2005,353(4):847-858
Tuberculosis kills about two million people every year and remains one of the leading causes of mortality worldwide. As a result of the increasing antibiotic resistance of Mycobacterium tuberculosis (Mtb) strains, there is an urgent need for new antitubercular drugs. Several efficient antibiotics, including isoniazid, specifically target the fatty acid synthase-II (FAS-II) complex of mycolic acid biosynthesis. We have previously shown that there are protein-protein interactions between the components of FAS-II that are essential for mycobacterial survival. We have now looked at the potential partners of FAS-II, mtFabD, the methyltransferases MmaAs, and Pks13. A combination of yeast two-hybrid and co-immunoprecipitation experiments showed that mtFabD interacts with each beta-ketoacyl-synthase (KasA, KasB and mtFabH) and with the core of FAS-II (InhA and MabA). The methyltransferases have a greater affinity for KasA and KasB than for mtFabH, suggesting that modifications on the meromycolic chains may occur during their elongation. Finally, Pks13, which catalyzes the final Claisen condensation of mycolic acids, interacts specifically with KasB. These data allowed us to determine the architecture of the multiple specialized FAS-II complexes, giving us insights into the organization of the complete mycolic acids biosynthesis. Our studies suggest a new and crucial interaction (KasB-Pks13) as a putative target for peptidomimetic antibiotics. 相似文献
973.
Roberta Besio Maria Camilla Baratto Roberta Gioia Enrico Monzani Stefania Nicolis Lucia Cucca Antonella Profumo Luigi Casella Riccardo Basosi Ruggero Tenni Antonio Rossi Antonella Forlino 《Biochimica et Biophysica Acta - Proteins and Proteomics》2013,1834(1):197-204
Human prolidase, the enzyme responsible for the hydrolysis of the Xaa-Pro/Hyp peptide bonds, is a key player in the recycling of imino acids during the final stage of protein catabolism and extracellular matrix remodeling. Its metal active site composition corresponding to the maximal catalytic activity is still unknown, although prolidase function is of increasing interest due to the link with carcinogenesis and mutations in prolidase gene cause a severe connective tissue disorder. Here, using EPR and ICP-MS on human recombinant prolidase produced in Escherichia coli (hRecProl), the Mn(II) ion organized in a dinuclear Mn(II)–Mn(II) center was identified as the protein cofactor. Furthermore, thermal denaturation, CD/fluorescence spectroscopy and limited proteolysis revealed that the Mn(II) is required for the proper protein folding and that a protein conformational modification is needed in the transition from apo- to Mn(II)loaded-enzyme. The collected data provided a better knowledge of the human holo-prolidase and, although limited to the recombinant enzyme, the exact identity and organization of the metal cofactor as well as the conformational change required for activity were proven. 相似文献
974.
Stefania Ondei Lynda D. Prior Grant J. Williamson Tom Vigilante David M. J. S. Bowman 《Ecology and evolution》2017,7(5):1592-1604
The small rainforest fragments found in savanna landscapes are powerful, yet often overlooked, model systems to understand the controls of these contrasting ecosystems. We analyzed the relative effect of climatic variables on rainforest density at a subcontinental level, and employed high‐resolution, regional‐level analyses to assess the importance of landscape settings and fire activity in determining rainforest density in a frequently burnt Australian savanna landscape. Estimates of rainforest density (ha/km2) across the Northern Territory and Western Australia, derived from preexisting maps, were used to calculate the correlations between rainforest density and climatic variables. A detailed map of the northern Kimberley (Western Australia) rainforests was generated and analyzed to determine the importance of geology and topography in controlling rainforests, and to contrast rainforest density on frequently burnt mainland and nearby islands. In the northwestern Australian, tropics rainforest density was positively correlated with rainfall and moisture index, and negatively correlated with potential evapotranspiration. At a regional scale, rainforests showed preference for complex topographic positions and more fertile geology. Compared with mainland areas, islands had significantly lower fire activity, with no differences between terrain types. They also displayed substantially higher rainforest density, even on level terrain where geomorphological processes do not concentrate nutrients or water. Our multi‐scale approach corroborates previous studies that suggest moist climate, infrequent fires, and geology are important stabilizing factors that allow rainforest fragments to persist in savanna landscapes. These factors need to be incorporated in models to predict the future extent of savannas and rainforests under climate change. 相似文献
975.
Relationships between wetland ecotones and inshore water quality in the Ugandan coast of Lake Victoria 总被引:1,自引:0,他引:1
Andrés Cózar Nadia Bergamino Stefania Mazzuoli Nicholas Azza Luca Bracchini Arduino M. Dattilo Steven A. Loiselle 《Wetlands Ecology and Management》2007,15(6):499-507
Much of the lake shore in Lake Victoria is covered by extensive wetlands, often dominated by dense papyrus stands that extend
out over the lake waters. These wetlands, their extension and management play a role in the physical, chemical and biological
conditions of the inshore waters. Continuous transects along 180 km of shoreline together with spatial grids of sampling sites
in eight bays were performed in the Ugandan inshore waters in order to analyze the relationships between the wetland characteristics
and water quality. Measurements of extension of the wetland ecotones, water temperature (T), pH, Secchi disk depth (SD), dissolved
oxygen (DO), total nitrogen (TN), total phosphorous (TP), dissolved inorganic nitrogen (DIN), soluble reactive phosphorus
(SRP) and chlorophyll-a (CHL) were made in each sampling area. Data of T, pH and DO collected during the transects showed that the water characteristics
of the bays differ from the open shoreline. Moreover, the magnitude of these physical–chemical differences is strongly conditioned
by the dimension of the bordering wetlands. Bays with extensive wetlands ecotones were characterized by cooler, more acidic
and poorly oxygenated waters. TN : TP ratios and especially DIN : SRP ratios decreased with the wetland presence along the
coastline, showing a higher probability of N limitation in the inshore waters where large wetlands are present. Results point
to denitrification processes in the wetland ecotones as the cause of this trend. The distribution of CHL was found to be highest
in the presence of two significant point loading sources: a river (in Katonga Bay) and a major population centre (Kampala,
in Murchison Bay). The reduction of external P loading is shown as an important step in the management of the eutrophication
process of Lake Victoria inshore waters. 相似文献
976.
Oxidative stress, characterized by overproduction of reactive oxygen species (ROS), is a major feature of several pathological states. Indeed, many cancers and neurodegenerative diseases are accompanied by altered redox balance, which results from dysregulation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In this review, we consider the role of the intracellular chloride channel 1 (CLIC1) in microglial cells during oxidative stress. Following microglial activation, CLIC1 translocates from the cytosol to the plasma membrane where it promotes a chloride conductance. The resultant anionic current balances the excess charge extruded by the active NADPH oxidase, supporting the generation of superoxide by the enzyme. In this scenario, CLIC1 could be considered to act as both a second messenger and an executor. 相似文献
977.
Karol Fijałkowski Helena Masiuk Danuta Czernomysy‐Furowicz Jolanta Karakulska Paweł Nawrotek Aleksandra Paszkowska Magdalena Struk Stefania Giedrys‐Kalemba 《Microbiology and immunology》2013,57(10):674-683
This study evaluated the superantigen gene profiles, genetic relatedness and biological activity of exosecretions of 50 Staphylococcus aureus isolates obtained from milk of cows with clinical mastitis. Genomic relatedness of S. aureus was determined by pulsed field gel electrophoresis analysis of macro‐restricted chromosomes. The presence of genes encoding superantigens was confirmed by multiplex PCR. To study the biological activity of S. aureus exosecretions, the supernatants from bacterial liquid cultures were classified into three groups: those with leukotoxin‐like properties, those with superantigen‐like properties and those with no particular activity on leukocytes cultured in vitro. It was shown that all analyzed bacterial isolates belonged to the same clonal type and harbored the same combination of superantigen genes, namely sed, selj and ser. However, 22% of all isolates produced factors with superantigen‐like and 48% of them with leukotoxin‐like activities. Finally, although there were no detectable genetic differences between the analyzed bacterial isolates, the virulence factors secreted by them differed considerably. 相似文献
978.
Purification and Properties of Cytosolic Copper, Zinc Superoxide Dismutase from Watermelon (Citrullus vulgaris Schrad.) Cotyledons 总被引:2,自引:0,他引:2
Jos M. Palma Gabriela M. Pastori Pablo Bueno Stefania Distefano Luis A. Del Rí o 《Free radical research》1997,26(1):83-91
Cytosolic copperzinc-superoxide dismutase (CuZn-SOD I; EC 1.15.1.1) was purified to homogeneity from watermelon (Citrullus vulgaris Schrad.) cotyledons. The stepwise purification procedure consisted of acetone precipitation, batch anion-exchange chromatography, anion-exchange Fast Protein Liquid Chromatography, gel-filtration column chromatography, and affinity chromatography on concanavalin A-Sepharose. CuZn-SOD I was purified 310-fold with a yield of 12.6 micrograms enzyme per gram cotyledons, and had a specific activity of 3, 540 units per milligram protein. The relative molecular mass for cytosolic CuZn-SOD was 34000, and it was composed by two equal subunits of 16.3 kDa. CuZn-SOD I did not contain neutral carbohydrates in its molecule, and its ultraviolet and visible absorption spectra showed two absorption maxima at 254 nm and 580 nm. Metal analysis showed that the enzyme contained 1 gram-atom Cu and 1 gram-atom Zn per mole dimer. Cytosolic CuZn-SOD was recognized by the antibody against peroxisomal CuZn-SOD from watermelon cotyledons, and its enzymatic activity was inhibited by this antibody. By IEF (pH 4.2-4.9), using a new method for vertical slab gels set up in our laboratory, purified cytosolic CuZn-SOD was resolved into two equal isoforms with isoelectric points of 4.63 and 4.66. 相似文献
979.
Farina AR Cappabianca L DeSantis G Di Ianni N Ruggeri P Ragone M Merolle S Tonissen KF Gulino A Mackay AR 《FEBS letters》2011,585(20):3328-3336
980.
Thorsten Mosler H Irem Baymaz Justus F Grf Ivan Mikicic Georges Blattner Edward Bartlett Matthias Ostermaier Rossana Piccinno Jiwen Yang Andrea Voigt Marco Gatti Stefania Pellegrino Matthias Altmeyer Katja Luck Ivan Ahel Vassilis Roukos Petra Beli 《Nucleic acids research》2022,50(20):11600
PARP1 mediates poly-ADP-ribosylation of proteins on chromatin in response to different types of DNA lesions. PARP inhibitors are used for the treatment of BRCA1/2-deficient breast, ovarian, and prostate cancer. Loss of DNA replication fork protection is proposed as one mechanism that contributes to the vulnerability of BRCA1/2-deficient cells to PARP inhibitors. However, the mechanisms that regulate PARP1 activity at stressed replication forks remain poorly understood. Here, we performed proximity proteomics of PARP1 and isolation of proteins on stressed replication forks to map putative PARP1 regulators. We identified TPX2 as a direct PARP1-binding protein that regulates the auto-ADP-ribosylation activity of PARP1. TPX2 interacts with DNA damage response proteins and promotes homology-directed repair of DNA double-strand breaks. Moreover, TPX2 mRNA levels are increased in BRCA1/2-mutated breast and prostate cancers, and high TPX2 expression levels correlate with the sensitivity of cancer cells to PARP-trapping inhibitors. We propose that TPX2 confers a mitosis-independent function in the cellular response to replication stress by interacting with PARP1. 相似文献