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141.
Spina M Cuccioloni M Mozzicafreddo M Montecchia F Pucciarelli S Eleuteri AM Fioretti E Angeletti M 《Proteins》2008,72(1):240-251
Dihydrofolate reductase (DHFR) is a ubiquitous enzyme involved in major biological process, including DNA synthesis and cancer inhibition, and its modulation is the object of extensive structural, kinetic, and pharmacological studies. In particular, earlier studies showed that green tea catechins are powerful inhibitors of bovine liver and chicken liver DHFR. In this article, we report the results of inhibition kinetics for the enzyme from another source (DHFR from E. coli) exerted by (-)-epigallocatechingallate (EGCG). Using different analytical techniques, we reported that EGCG acts as a bisubstrate inhibitor on the bacterial DHFR. Moreover, the combined approach of biosensor, kinetic, and molecular modelling analysis disclosed the ability of EGCG to bind to the enzyme both on substrate (DHF) and cofactor (NADPH) site. Collectively, our data have confirmed the selectivity of antifolate compounds with respect to the different source of enzyme (bacterial or mammalian DHFR) and the possible role of tea catechins as chemopreventive agents. 相似文献
142.
Laura Bonfili Manila Amici Valentina Cecarini Massimiliano Cuccioloni Rosalia Tacconi Mauro Angeletti Evandro Fioretti Jeffrey N. Keller Anna Maria Eleuteri 《Biochimie》2009,91(9):1131-1144
Natural occurring modulators of proteasome functionality are extensively investigated for their implication in cancer therapy. On the basis of our previous evidences both on proteasomal inhibition by monomeric polyphenols, and on the characterization of wheat sprout hydroalcoholic extract, herein we thoroughly report on a comparative study of the effect of wheat sprout extract on both normal and tumour cells. Treatment of isolated 20S proteasomes with wheat sprout extracts induced a gradual inhibition of all proteasome activities. Next, two wheat sprout extract components were separated: a polyphenol and a protein fraction. Both components exerted an in vitro inhibitory effect on proteasome activity. HeLa tumour cells and FHs 74 Int normal cells were exposed to both fractions, resulting in different rates of proteasome inhibition, with tumour cells showing a significantly higher degree of proteasome impairment and apoptosis induction. Furthermore, a decrease in proteasome activities and in cell survival of the human plasmacytoma RPMI 8226 cell line, upon the same treatments, was observed. Collectively, our results provide additional evidences supporting the possible use of natural extracts as coadjuvants in cancer treatments. 相似文献
143.
Chronic gastro-oesophageal reflux disease can induce a metaplastic change of the distal oesophagus called Barrett’s oesophagus
whereby the normal squamous epithelium is substituted by a columnar epithelium. Patients with Barrett’s oesophagus are at
increased risk of oesophageal adenocarcinoma which occurs through dysplastic stages with increasing degree of cellular and
architectural disorganization. Barrett’s oesophagus represents an ideal model to study the genetic events supporting the onset
of an invasive tumour since patients with this condition are surveilled with endoscopic tissue sampling until high grade dysplasia
or intramucosal carcinoma develop. However, due to the relatively low incidence of this disease compared to other cancers,
i.e. colon and breast, it is only recently that researchers have concentrated on understanding the genetic events supporting
the onset of Barrett’s and its transformation to cancer. Here, we review the knowledge acquired so far on the genetic and
molecular alterations along the oesophageal metaplasia–dysplasia-carcinoma sequence. 相似文献
144.
Since teeth are resistant to decomposition processes, they provide important and at times unique sources of information about fossil humans. Fortunately, dental remains reflect significant evolutionary changes. These changes make a very important and often exclusive contribution to the definition of new taxa or the attribution of fossil specimens to existing taxa.The traditional approach to dental morphometric analyses usually focuses on the recording of several measures of the tooth with calipers, especially the two basic crown diameters (buccolingual and mesiodistal). However, since these measures do not adequately represent the complex morphology of the tooth, 2D images and 3D digital models of dental morphology have been used. For both types of analysis, the possibility of correctly comparing homologous teeth depends on the adoption of a common orientation system. The lack of such a system makes it difficult to compare the results of different studies.Here we describe a new method for orienting teeth specifically devised for the upper and lower first molar (M1). Samples of unworn maxillary (n = 15) and mandibular (n = 15) first molars of modern humans were scanned with a Roland Picza 3D digitizer. The 3D virtual models were used to compare our new orientation method with those proposed in the literature. The new orientation system, which meets a geometric criterion, is based on three points identified on the cervical line and ensures acceptable repeatability of the spatial positioning and orientation independent of the shape and wear of the first molar under investigation. This orientation system is a first step toward the creation of a virtual set of hominid and fossil human first molars, which will allow us to make comparisons via a sophisticated and noninvasive approach. This pilot study also provides guidelines to extend the new methodology to the other types of teeth. 相似文献
145.
Sara Cesarini Andrea Spallarossa Angelo Ranise Olga Bruno Nicoletta Arduino Maria Bertolotto Franco Dallegri Massimiliano Tognolini Thomas Gobbetti Elisabetta Barocelli 《Bioorganic & medicinal chemistry》2009,17(10):3580-3587
A series of 6-amino-4-oxo-1,3-diphenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonyl derivatives was synthesized. The compounds demonstrated to be novel, potent and selective inhibitors of Interleukin-8-induced human neutrophil chemotaxis. A SAR study was performed by varying the carbonyl function at position 5 and the chain linked to the amino group at position 6 of the scaffold. All the compounds of the series displayed inhibitory activity at nano- or picomolar concentrations against Interleukin-8-driven migration and no activity against fMLP- and C5a-induced chemotaxis. The binding tests of selected compounds on CXCR1 and CXCR2 receptors were negative. The most potent derivative showed in vivo efficacy in a mouse model of Zymosan-induced peritonitis. 相似文献
146.
Alessandra Pesce Liesbet Thijs Marco Nardini Lorenza Sisinni Louise Gourlay Massimiliano Coletta Xuehua Wan Paolo Ascenzi Martino Bolognesi 《Journal of molecular biology》2009,386(1):246-35534
Among heme-based sensors, recent phylogenomic and sequence analyses have identified 34 globin coupled sensors (GCS), to which an aerotactic or gene-regulating function has been tentatively ascribed. Here, the structural and biochemical characterization of the globin domain of the GCS from Geobacter sulfurreducens (GsGCS162) is reported. A combination of X-ray crystallography (crystal structure at 1.5 Å resolution), UV-vis and resonance Raman spectroscopy reveals the ferric GsGCS162 as an example of bis-histidyl hexa-coordinated GCS. In contrast to the known hexa-coordinated globins, the distal heme-coordination in ferric GsGCS162 is provided by a His residue unexpectedly located at the E11 topological site. Furthermore, UV-vis and resonance Raman spectroscopy indicated that ferrous deoxygenated GsGCS162 is a penta-/hexa-coordinated mixture, and the heme hexa-to-penta-coordination transition does not represent a rate-limiting step for carbonylation kinetics. Lastly, electron paramagnetic resonance indicates that ferrous nitrosylated GsGCS162 is a penta-coordinated species, where the proximal HisF8-Fe bond is severed. 相似文献
147.
Massimiliano Baldassarre Ziba Razinia Clara F. Burande Isabelle Lamsoul Pierre G. Lutz David A. Calderwood 《PloS one》2009,4(11)
Mammalian filamins (FLNs) are a family of three large actin-binding proteins. FLNa, the founding member of the family, was implicated in migration by cell biological analyses and the identification of FLNA mutations in the neuronal migration disorder periventricular heterotopia. However, recent knockout studies have questioned the relevance of FLNa to cell migration. Here we have used shRNA-mediated knockdown of FLNa, FLNb or FLNa and FLNb, or, alternatively, acute proteasomal degradation of all three FLNs, to generate FLN-deficient cells and assess their ability to migrate. We report that loss of FLNa or FLNb has little effect on migration but that knockdown of FLNa and FLNb, or proteolysis of all three FLNs, impairs migration. The observed defect is primarily a deficiency in initiation of motility rather than a problem with maintenance of locomotion speed. FLN-deficient cells are also impaired in spreading. Re-expression of full length FLNa, but not re-expression of a mutated FLNa lacking immunoglobulin domains 19 to 21, reverts both the spreading and the inhibition of initiation of migration.Our results establish a role for FLNs in cell migration and spreading and suggest that compensation by other FLNs may mask phenotypes in single knockout or knockdown cells. We propose that interactions between FLNs and transmembrane or signalling proteins, mediated at least in part by immunoglobulin domains 19 to 21 are important for both cell spreading and initiation of migration. 相似文献
148.
Massimiliano Virgilio Thierry Backeljau Bruno Nevado Marc De Meyer 《BMC bioinformatics》2010,11(1):206
Background
Previous studies on insect DNA barcoding provide contradictory results and suggest not consistent performances across orders. This work aims at providing a general evaluation of insect DNA barcoding and "mini-barcoding" by performing simulations on a large database of 15,948 DNA barcodes. We compared the proportions of correctly identified queries across a) six insect orders (Coleoptera, Diptera, Hemiptera, Hymenoptera, Lepidoptera and Orthoptera), b) four identification criteria (Best Match: BM; Best Close Match: BCM; All Species Barcodes: ASB; tree-based identification: NJT), and c) reference databases with different taxon coverage (100, 500, 1,000, 1,500 and 1,995 insect species). 相似文献149.
Emanuela Giombini Massimiliano Orsini Danilo Carrabino Anna Tramontano 《BMC bioinformatics》2010,11(1):39
Background
Bacterial infections represent a global health challenge. The identification of novel antibacterial targets for both therapy and vaccination is needed on a constant basis because resistance continues to spread worldwide at an alarming rate. Even infections that were once easy to treat are becoming difficult or, in some cases, impossible to cure. Ideal targets for both therapy and vaccination are bacterial proteins exposed on the surface of the organism, which are often involved in host-pathogen interaction. Their identification can greatly benefit from technologies such as bioinformatics, proteomics and DNA microarrays. 相似文献150.
Prosperi MC De Luca A Di Giambenedetto S Bracciale L Fabbiani M Cauda R Salemi M 《PloS one》2010,5(10):e13619