Silvio C. E. Tosatto

@article{SCOPUS_ID:74249088516,

title = {Global and local model quality estimation at CASP8 using the scoring functions QMEAN and QMEANclust},

author = {Pascal Benkert and Silvio C. E. Tosatto and Torsten Schwede},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-74249088516&origin=inward},

doi = {10.1002/prot.22532},

year  = {2009},

date = {2009-01-01},

journal = {Proteins: Structure, Function and Bioinformatics},

volume = {77},

number = {SUPPL. 9},

pages = {173-180},

abstract = {Identifying the best candidate model among an ensemble of alternatives is crucial in protein structure prediction. For this purpose, scoring functions have been developed which either calculate a quality estimate on the basis of a single model or derive a score from the information contained in the ensemble of models generated for a given sequence (i.e., consensus methods). At CASP7, consensus methods have performed considerably better than scoring functions operating on single models. However, consensus methods tend to fail if the best models are far from the center of the dominant structural cluster. At CASP8, we investigated whether our hybrid method QMEANclust may overcome this limitation by combining the QMEAN composite scoring function operating on single models with consensus information. We participated with four different scoring functions in the quality assessment category. The QMEANclust consensus scoring function turned out to be a successful method both for the ranking of entire models but especially for the estimation of the per-residue model quality. In this article, we briefly describe the two scoring functions QMEAN and QMEANclust and discuss their performance in the context of what went right and wrong at CASP8. Both scoring functions are publicly available at http://swissmodel. expasy.org/qmean/. © 2009 WILEY-LISS, INC.},

note = {Cited by: 53},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:67650104280,

title = {Electric dipole reorientation in the interaction of botulinum neurotoxins with neuronal membranes},

author = {Federico Fogolari and Silvio C. E. Tosatto and Lucia Muraro and Cesare Montecucco},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-67650104280&origin=inward},

doi = {10.1016/j.febslet.2009.06.046},

year  = {2009},

date = {2009-01-01},

journal = {FEBS Letters},

volume = {583},

number = {14},

pages = {2321-2325},

abstract = {Botulinum neurotoxins are highly potent toxins capable of rapid and specific interaction with the presynaptic membrane. We have hypothesised that: (1) these neurotoxins possess an electric dipole with the positive pole on receptor binding domain Hc-C and that (2) on approaching the negatively charged presynaptic membrane, they reorient themselves and hit the membrane surface with Hc-C; this electrostatic effect would contribute efficient binding. Electrostatic calculations confirm these hypotheses and strongly indicate that electrostatics effects can play an important role in the unique presynaptic membrane binding properties of these neurotoxins and generally on the interaction of other plasma membrane protein ligands. © 2009.},

note = {Cited by: 19; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:66349088076,

title = {REPETITA: Detection and discrimination of the periodicity of protein solenoid repeats by discrete Fourier transform},

author = {Luca Marsella and Francesco Sirocco and Antonio Trovato and Flavio Seno and Silvio C. E. Tosatto},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-66349088076&origin=inward},

doi = {10.1093/bioinformatics/btp232},

year  = {2009},

date = {2009-01-01},

journal = {Bioinformatics},

volume = {25},

number = {12},

publisher = {Oxford University Press},

abstract = {Motivation: Proteins with solenoid repeats evolve more quickly than non-repetitive ones and their periodicity may be rapidly hidden at sequence level, while still evident in structure. In order to identify these repeats, we propose here a novel method based on a metric characterizing amino-acid properties (polarity, secondary structure, molecular volume, codon diversity, electric charge) using five previously derived numerical functions. Results: The five spectra of the candidate sequences coding for structural repeats, obtained by Discrete Fourier Transform (DFT), show common features allowing determination of repeat periodicity with excellent results. Moreover it is possible to introduce a phase space parameterized by two quantities related to the Fourier spectra which allow for a clear distinction between a non-homologous set of globular proteins and proteins with solenoid repeats. The DFT method is shown to be competitive with other state of the art methods in the detection of solenoid structures, while improving its performance especially in the identification of periodicities, since it is able to recognize the actual repeat length in most cases. Moreover it highlights the relevance of local structural propensities in determining solenoid repeats. © 2009 The Author(s).},

note = {Cited by: 59; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:40549141792,

title = {QMEAN: A comprehensive scoring function for model quality assessment},

author = {Pascal Benkert and Silvio C. E. Tosatto and Dietmar Schomburg},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-40549141792&origin=inward},

doi = {10.1002/prot.21715},

year  = {2008},

date = {2008-01-01},

journal = {Proteins: Structure, Function and Genetics},

volume = {71},

number = {1},

pages = {261-277},

abstract = {In protein structure prediction, a considerable number of alternative models are usually produced from which subsequently the final model has to be selected. Thus, a scoring function for the identification of the best model within an ensemble of alternative models is a key component of most protein structure prediction pipelines. QMEAN, which stands for Qualitative Model Energy ANalysis, is a composite scoring function describing the major geometrical aspects of protein structures. Five different structural descriptors are used. The local geometry is analyzed by a new kind of torsion angle potential over three consecutive amino acids. A secondary structure-specific distance-dependent pairwise residue-level potential is used to assess long-range interactions. A solvation potential describes the burial status of the residues. Two simple terms describing the agreement of predicted and calculated secondary structure and solvent accessibility, respectively, are also included. A variety of different implementations are investigated and several approaches to combine and optimize them are discussed. QMEAN was tested on several standard decoy sets including a molecular dynamics simulation decoy set as well as on a comprehensive data set of totally 22,420 models from server predictions for the 95 targets of CASP7. In a comparison to five well-established model quality assessment programs, QMEAN shows a statistically significant improvement over nearly all quality measures describing the ability of the scoring function to identify the native structure and to discriminate good from bad models. The three-residue torsion angle potential turned out to be very effective in recognizing the native fold. © 2007 Wiley-Liss, Inc.},

note = {Cited by: 905},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:43449113547,

title = {Inhibitory interaction of the 14-3-3 proteins with ubiquitous (PMCA1) and tissue-specific (PMCA3) isoforms of the plasma membrane Ca2+ pump},

author = {Cristina I. Linde and Francesca Di Leva and Teuta Domi and Silvio C. E. Tosatto and Marisa Brini and Ernesto Carafoli},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-43449113547&origin=inward},

doi = {10.1016/j.ceca.2007.09.003},

year  = {2008},

date = {2008-01-01},

journal = {Cell Calcium},

volume = {43},

number = {6},

pages = {550-561},

publisher = {Elsevier Ltd},

abstract = {A previous study has demonstrated that the ubiquitous plasma membrane Ca2+ pump PMCA4 interacted with isoform ε of the 14-3-3 protein, whereas the nervous tissue-specific PMCA2 did not. The 14-3-3 proteins are widely expressed small acidic proteins, which modulate cell signaling, intracellular trafficking, transcription and apoptosis. The investigation has been extended to the other tissue-restricted pump (PMCA3) and to the other ubiquitous pump (PMCA1). At variance with PMCA2, PMCA3 interacted with the 14-3-3ε protein in a two-hybrid system assay, which could not be used for PMCA1. The 14-3-3ε protein immunoprecipitated with both PMCA3 and PMCA1 when expressed in HeLa cells. Pull-down experiments using GST-PMCA1 and GST-PMCA3 fusion products confirmed the interaction of both pumps with the 14-3-3ε protein. The binding was phosphorylation-independent with both PMCA3 and PMCA1. The 14-3-3ζ isoform also interacted with PMCA3; however, it did not interact with PMCA1. The effect of the interaction on the activity of the two pumps, and thus on the homeostasis of Ca2+, was investigated by co-expressing the 14-3-3ε protein and PMCA3 or PMCA1 in CHO cells together with the recombinant Ca2+ indicator aequorin: the ability of cells to re-establish the basal Ca2+ concentration following a Ca2+ transient induced by an InsP3-producing agonist was substantially decreased with both pumps, indicating that the interaction with the 14-3-3 protein inhibited the activity of both PMCA3 and PMCA1. © 2007 Elsevier Ltd. All rights reserved.},

note = {Cited by: 37},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:55749104577,

title = {TESE: Generating specific protein structure test set ensembles},

author = {Francesco Sirocco and Silvio C. E. Tosatto},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-55749104577&origin=inward},

doi = {10.1093/bioinformatics/btn488},

year  = {2008},

date = {2008-01-01},

journal = {Bioinformatics},

volume = {24},

number = {22},

pages = {2632-2633},

abstract = {Summary: TESE is a web server for the generation of test sets of protein sequences and structures fulfilling a number of different criteria. At least three different use cases can be envisaged: (i) benchmarking of novel methods; (ii) test sets tailored for special needs and (iii) extending available datasets. The CATH structure classification is used to control structural/sequence redundancy and a variety of structural quality parameters can be used to interactively select protein subsets with specific characteristics, e.g. all X-ray structures of α-helical repeat proteins with more than 120 residues and resolution <2.0 Å. The output includes FASTA-formatted sequences, PDB files and a clickable HTML index file containing images of the selected proteins. Multiple subsets for cross-validation are also supported. © The Author 2008. Published by Oxford University Press. All rights reserved.},

note = {Cited by: 10; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:46449103532,

title = {Evolutionary and structural insights into the multifaceted glutathione peroxidase (Gpx) superfamily},

author = {Stefano Toppo and Stefano Vanin and Valentina Bosello and Silvio C. E. Tosatto},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-46449103532&origin=inward},

doi = {10.1089/ars.2008.2057},

year  = {2008},

date = {2008-01-01},

journal = {Antioxidants and Redox Signaling},

volume = {10},

number = {9},

pages = {1501-1513},

abstract = {Glutathione peroxidase (GPx) is a widespread protein superfamily found in many organisms throughout all kingdoms of life. Although it was initially thought to use only glutathione as reductant, recent evidence suggests that the majority of GPxs have specificity for thioredoxin. We present a thorough in silico analysis performed on 724 sequences and 12 structures aimed to clarify the evolutionary, structural, and sequence determinants of GPx specificity. Structural variability was found to be limited to only two regions, termed oligomerization loop and functional helix, which modulate both reduced substrate specificity and oligomerization state. We show that mammalian GPx-1, the canonic selenocysteine-based tetrameric glutathione peroxidase, is a recent "invention" during evolution. Contrary to common belief, cysteine-based thioredoxin-specific GPx, which we propose the TGPx, are both more common and more ancient. This raises interesting evolutionary considerations regarding oligomerization and the use of active-site selenocysteine residue. In addition, phylogenetic analysis has revealed the presence of a novel member belonging to the GPx superfamily in Mammalia and Amphibia, for which we propose the name GPx-8, following the present numeric order of the mammalian GPxs. © Mary Ann Liebert, Inc. 2008.},

note = {Cited by: 228},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:38849180102,

title = {Comparative analysis of [FeFe] hydrogenase from Thermotogales indicates the molecular basis of resistance to oxygen inactivation},

author = {Silvio C. E. Tosatto and Stefano Toppo and Donatella Carbonera and Giorgio M. Giacometti and Paola Costantini},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-38849180102&origin=inward},

doi = {10.1016/j.ijhydene.2007.10.010},

year  = {2008},

date = {2008-01-01},

journal = {International Journal of Hydrogen Energy},

volume = {33},

number = {2},

pages = {570-578},

publisher = {Elsevier Ltd},

abstract = {Several Thermotogales, previously reported as being strict anaerobes, have demonstrated the ability to grow and produce hydrogen in the presence of moderate amounts of molecular oxygen. Thermotoga neapolitana seems to be less sensitive to O2 than other members of this order, including Thermotoga maritima, whose hydrogenase has been purified and characterized. Instead, the enzyme responsible for the hydrogen production by T. neapolitana has not yet been identified. After the recent sequencing of the T. neapolitana genome, it has been possible to search for the orthologous gene responsible for this unusal hydrogenase activity. By means of in silico analysis, we built a molecular model for both T. maritima and T. neapolitana proteins and analyzed conservation, focusing on the subtle structural differences responsible for the increased oxygen resistance in the latter and underscoring two mutations (E475S and T539L) which represent a specific adaption for more effective release of hydrogen in aerobic conditions. © 2007 International Association for Hydrogen Energy.},

note = {Cited by: 18; Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:46749140860,

title = {Low density lipoprotein misfolding and amyloidogenesis},

author = {Tiziana Parasassi and Marco De Spirito and Giampiero Mei and Roberto Brunelli and Giulia Greco and Laura Lenzi and Giuseppe Maulucci and Eleonora Nicolai and Massimiliano Papi and Giuseppe Arcovito and Silvio C. E. Tosatto and Fulvio Ursini},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-46749140860&origin=inward},

doi = {10.1096/fj.07-097774},

year  = {2008},

date = {2008-01-01},

journal = {FASEB Journal},

volume = {22},

number = {7},

pages = {2350-2356},

abstract = {In early atherogenesis, subendothelial retention of lipidic droplets is associated with an inflammatory response-to-injury, culminating in the formation of foam cells and plaque. Low density lipoprotein (LDL) is the main constituent of subendothelial lipidic droplets. The process is believed to occur following LDL modification. Searching for a modified LDL in plasma, electronegative LDL [LDL(-)] was identified and found to be associated with major risk biomarkers. The apoprotein in LDL(-) is misfolded, and we show here that this modification primes the aggregation of native LDL, conforming to the typical pattern of protein amyloidogenesis. After a lag phase, whose length depends on LDL(-) concentration, light scattering and atomic force microscopy reveal early exponential growth of intermediate globules, which evolve into fibrils. These globules are remarkably similar to subendothelial droplets in atheromatous lesions and different from those produced by oxidation or biochemical manipulation. During aggregation, ellipticity and tryptophan fluorescence measurements reveal a domino-style spread of apoprotein misfolding from LDL(-) to all of the LDL. Computational analysis of the apoprotein primary sequence predicts an unstable, aggregation-prone domain in the regulatory α2 region. Apoprotein misfolding well represents an LDL modification able to transform this cholesterol carrier into a trigger for a response-to-injury in the artery wall. © FASEB.},

note = {Cited by: 47},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SCOPUS_ID:46449138673,

title = {The catalytic site of glutathione peroxidases},

author = {Silvio C. E. Tosatto and Valentina Bosello and Federico Fogolari and Pierluigi Mauri and Antonella Roveri and Stefano Toppo and Leopold Flohé and Fulvio Ursini and Matilde Maiorino},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-46449138673&origin=inward},

doi = {10.1089/ars.2008.2055},

year  = {2008},

date = {2008-01-01},

journal = {Antioxidants and Redox Signaling},

volume = {10},

number = {9},

pages = {1515-1525},

abstract = {In GPxs, the redox-active Se or S, is at hydrogen bonding distance from Gln and Trp residues that contribute to catalysis. From sequence homology of >400 sequences and modeling of the DmGPx as a paradigm, Asn136 emerged as a fourth essential component of the active site. Mutational substitution of Asn136 by His, Ala, or Asp results in a dramatic decline of specific activity. Kinetic analysis indicates that k+1, the rate constant for the oxidation of the enzyme, decreases by two to three orders of magnitude, whereas the reductive steps characterized by k′+2 are less affected. Accordingly, MS/MS analysis shows that in Asn136 mutants, the peroxidatic Cys45 stays largely reduced also in the presence of a hydroperoxide, whereas in the wild-type enzyme, it is oxidized, forming a disulfide with the resolving Cys. Computational calculation of pKa values indicates that the residues facing the catalytic thiol, Asn136, Gln80, and, to a lesser extent Trp135, contribute to the dissociation of the thiol group, Asn136 being most relevant. These data disclose that the catalytic site of GPxs has to be redrawn as a tetrad, including Asn136, and suggest a mechanism accounting for the extraordinary catalytic efficiency of GPxs. © Mary Ann Liebert, Inc. 2008.},

note = {Cited by: 166},

keywords = {},

pubstate = {published},

tppubtype = {article}

}