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71.
Differential requirement for the ATPase domain of the Cockayne syndrome group B gene in the processing of UV-induced DNA damage and 8-oxoguanine lesions in human cells 总被引:1,自引:2,他引:1 下载免费PDF全文
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Gaetano Barbato Daniel O. Cicero Elisabetta Bianchi Antonello Pessi Renzo Bazzo 《Journal of biomolecular NMR》1996,8(1):36-48
Summary We describe the high-resolution structure by NMR of two peptides that belong to a combinatorial library based on the zinc-finger motif. The library represents, to the best of our knowledge, the first example of a conformationally homogeneous peptide library and was obtained by introducing random residues in five positions of the -helical portion of a 26-residue consensus peptide (CP1) belonging to the Cys2-Hys2 zinc-finger family. The result was shown to be a highly homogeneous -helical library (Bianchi et al., 1995). The structures of the parent compound (CP1) and of a representative member (CP1m) that was selected by screening the library with a monoclonal antibody are compared in detail as an example of the very high stability of the zinc-finger scaffold upon sequence variability. The two peptides exhibit an extremely high degree of structural similarity. The use of this type of conformationally constrained combinatorial library might represent a step forward in the design of peptidomimetics, as it considerably accelerates the process of the identification of the spatial relationship among the pharmacophoric groups.Abbreviations
t-Bu
tert-butyloxycarbonyl
- Fmoc
9-fluorenylmethoxycarbonyl 相似文献
77.
Daniele Repetto Simona Aramu Elisabetta Boeri Erba Nanaocha Sharma Silvia Grasso Isabella Russo Ole N. Jensen Sara Cabodi Emilia Turco Paola Di Stefano Paola Defilippi 《PloS one》2013,8(1)
Protein phosphorylation tightly regulates specific binding of effector proteins that control many diverse biological functions of cells (e. g. signaling, migration and proliferation). p140Cap is an adaptor protein, specifically expressed in brain, testis and epithelial cells, that undergoes phosphorylation and tunes its interactions with other regulatory molecules via post-translation modification. In this work, using mass spectrometry, we found that p140Cap is in vivo phosphorylated on tyrosine (Y) within the peptide GEGLpYADPYGLLHEGR (from now on referred to as EGLYA) as well as on three serine residues. Consistently, EGLYA has the highest score of in silico prediction of p140Cap phosphorylation. To further investigate the p140Cap function, we performed site specific mutagenesis on tyrosines inserted in EGLYA and EPLYA, a second sequence with the same highest score of phosphorylation. The mutant protein, in which both EPLYA/EGLYA tyrosines were converted to phenylalanine, was no longer tyrosine phosphorylated, despite the presence of other tyrosine residues in p140Cap sequence. Moreover, this mutant lost its ability to bind the C-terminal Src kinase (Csk), previously shown to interact with p140Cap by Far Western analysis. In addition, we found that in vitro and in HEK-293 cells, the Abelson kinase is the major kinase involved in p140Cap tyrosine phosphorylation on the EPLYA and EGLYA sequences. Overall, these data represent an original attempt to in vivo characterise phosphorylated residues of p140Cap. Elucidating the function of p140Cap will provide novel insights into its biological activity not only in normal cells, but also in tumors. 相似文献
78.
Tiziana Cabras Elisabetta Pisano Caterina Montaldo Maria Rita Giuca Federica Iavarone Giuseppe Zampino Massimo Castagnola Irene Messana 《Molecular & cellular proteomics : MCP》2013,12(7):1844-1852
People with Down syndrome, a frequent genetic disorder in humans, have increased risk of health problems associated with this condition. One clinical feature of Down syndrome is the increased prevalence and severity of periodontal disease in comparison with the general population. Because saliva plays an important role in maintaining oral health, in the present study the salivary proteome of Down syndrome subjects was investigated to explore modifications with respect to healthy subjects. Whole saliva of 36 Down syndrome subjects, divided in the age groups 10–17 yr and 18–50 yr, was analyzed by a top-down proteomic approach, based on the high performance liquid chromatography-electrospray ionization–MS analysis of the intact proteins and peptides, and the qualitative and quantitative profiles were compared with sex- and age-matched control groups. The results showed the following interesting features: 1) as opposed to controls, in Down syndrome subjects the concentration of the major salivary proteins of gland origin did not increase with age; as a consequence concentration of acidic proline rich proteins and S cystatins were found significantly reduced in older Down syndrome subjects with respect to matched controls; 2) levels of the antimicrobial α-defensins 1 and 2 and histatins 3 and 5 were significantly increased in whole saliva of older Down syndrome subjects with respect to controls; 3) S100A7, S100A8, and S100A12 levels were significantly increased in whole saliva of Down syndrome subjects in comparison with controls. The increased level of S100A7 and S100A12 may be of particular interest as a biomarker of early onset Alzheimer''s disease, which is frequently associated with Down syndrome.Down syndrome (DS)1 is a frequent genetic disorder in humans characterized by premature aging (1). A clinical feature of people with DS is the increased prevalence and severity of periodontal disease compared with age-matched subjects of similar levels of intellectual impairment and compared with the general population (2). Common conditions observed in DS are marginal gingivitis, acute and subacute necrotizing gingivitis, advanced periodontitis, gingival recession, and pocket formation (3, 4). It is known that saliva plays an important role in maintaining oral and dental health, because of the presence of a variety of antimicrobial peptides mainly derived from gland secretion, oral epithelial cells, and neutrophils (5). Several papers reported that neutrophils and T-lymphocyte function is impaired in people with DS (6–9). However, the salivary secretion of the antimicrobial LL-37 in young individuals with DS was found normal (10). A review of the literature (11, 12) reveals only sporadic and contradictory reports that attempt to explain the role of saliva in the oral health of subjects with DS, and on the whole, information on the biochemical composition of their saliva is scarce. On the basis of the above information, in the present study, we proposed to investigate the salivary proteome of DS subjects by an intact protein-based “top-down” approach. The spectrum of salivary peptides of DS subjects was compared with that of sex and age-matched healthy control groups to determine qualitative and quantitative differences. Interestingly, the results showed that several members of the S100A family, which possess different biological functions, and also described as potential markers of the Alzheimer Disease, were significantly increased in saliva of Down syndrome subjects with respect to controls. 相似文献
79.
Vanessa Castelli Francesco Melani Claudio Ferri Michele d'Angelo Mariano Catanesi Davide Grassi Elisabetta Benedetti Antonio Giordano Annamaria Cimini Giovambattista Desideri 《Journal of cellular biochemistry》2020,121(12):4862-4869
Oxidative stress is considered the common effector of the cascade of degenerative events in many neurological conditions. Thus, in this paper we tested different nutraceuticals in H2O2 in vitro model to understand if could represent an adjuvant treatment for neurological diseases. In this study, nutraceuticals bacopa, lycopene, astaxanthin, and vitamin B12 were used alone or in combination in human neuronal differentiated SH-SY5Y cells upon hydrogen peroxide-induced injury and neuroprotective, neuronal death pathways were analyzed. The nutraceuticals analyzed were able to protect H2O2 cytotoxic effects, through increasing cell viability and proteins involved in neuroprotection pathways and restoring proteins involved in cell death pathways. On this basis, it is possible to propose the use of these compounds as dietary supplement for the prevention or as adjuvant to the only symptomatic treatments so far available for neurodegenerative diseases. 相似文献
80.
Kohen W. Bauer N. Ryan McKenzie Cinzia Bottini Elisabetta Erba Sean A. Crowe 《Geobiology》2023,21(3):341-354
Oceanic Anoxic Events (OAEs) are conspicuous intervals in the geologic record that are associated with the deposition of organic carbon (OC)-rich marine sediment, linked to extreme biogeochemical perturbations, and characterized by widespread ocean deoxygenation. Mechanistic links between the marine biological carbon pump (BCP), redox conditions, and organic carbon burial during OAEs, however, remain poorly constrained. In this work we reconstructed the BCP in the western Tethys Ocean across OAE1a (~120 Mya) using sediment geochemistry and OC mass accumulation rates (OCAcc). We find that OCAcc were between 0.006 and 3.3 gC m−2 yr−1, with a mean value of 0.79 ± 0.78 SD gC m−2 yr−1—these rates are low and comparable to oligotrophic regions in the modern oceans. This challenges longstanding assumptions that oceanic anoxic events are intervals of strongly elevated organic carbon burial. Numerical modelling of the BCP, furthermore, reveals that such low OC fluxes are only possible with either or both low to moderate OC export fluxes from ocean surface waters, with rates similar to oligotrophic (nutrient-poor, <30 gC m−2 yr−1) and mesotrophic (moderate-nutrients, ~50–100 gC m−2 yr−1) regions in the modern ocean, and stronger than modern vertical OC attenuation. The low OC fluxes thus reflect a relatively weak BCP. Low to moderate productivity is further supported by palaeoecological and geochemical evidence and was likely maintained through nutrient limitation that developed in response to the burial and sequestration of phosphorus in association with iron minerals under ferruginous (anoxic iron-rich) ocean conditions. Without persistently high productivity, ocean deoxygenation during OAE1a was more likely driven by other physicochemical and biological factors including ocean warming, changes in marine primary producer community composition, and fundamental shifts in the efficiency of the BCP with associated effects and feedbacks. 相似文献