Biomedical subjects

Giulio Gianese

Publications and source records attributed to Giulio Gianese.

5 recordsLinked to original sources

PubMed2006

A consensus procedure improving solvent accessibility prediction.

Prediction methods of structural features in 1D represent a useful tool for the understanding of folding, classification, and function of proteins, and, in particular, for 3D structure prediction. Among the structural aspects characterizing a protein, solvent accessibility has received great attention in recent years. The available methods proposed for predicting accessibility have never considered the combination of the results deriving from different methods to construct a consensus prediction able to provide more reliable results. A consensus approach that increases prediction accuracy using three high-performance methods is described. The results of our method for three different protein data sets show that up to 3.0% improvement in prediction accuracy of solvent accessibility may be obtained by a consensus approach. The improvement also extends to the correlation coefficient. Application of our consensus approach to the accessibility prediction using only three prediction methods gives results better than single methods combined for consensus formation. Currently, the scarce availability of predictors with similar parameters defining solvent accessibility hinders the testing of other methods in our consensus procedure.

Amino Acid Sequence↗

PubMed2005

Calcium-induced tertiary structure modifications of endo-beta-1,3-glucanase from Pyrococcus furiosus in 7.9 M guanidinium chloride.

The family 16 endo-beta-1,3 glucanase from the extremophilic archaeon Pyrococcus furiosus is a laminarinase, which in 7.9 M GdmCl (guanidinium chloride) maintains a significant amount of tertiary structure without any change of secondary structure. The addition of calcium to the enzyme in 7.9 M GdmCl causes significant changes to the near-UV CD and fluorescence spectra, suggesting a notable increase in the tertiary structure which leads to a state comparable, but not identical, to the native state. The capability to interact with calcium in 7.9 M GdmCl with a consistent recovery of native tertiary structure is a unique property of this extremely stable endo-beta-1,3 glucanase. The effect of calcium on the thermodynamic parameters relative to the GdmCl-induced equilibrium unfolding has been analysed by CD and fluorescence spectroscopy. The interaction of calcium with the native form of the enzyme is studied by Fourier-transform infrared spectroscopy in the absorption region of carboxylate groups and by titration in the presence of a chromophoric chelator. A homology-based model of the enzyme is generated and used to predict the putative binding site(s) for calcium and the structural interactions potentially responsible for the unusual stability of this protein, in comparison with other family 16 glycoside hydrolases.

Amino Acid Sequence↗

PubMed2003

Structural plasticity of thermophilic serine hydroxymethyltransferases.

Serine hydroxymethyltransferase (SHMT) catalyzes the reversible cleavage of serine to form glycine and monocarbonic groups, essential in several biosynthetic pathways. The availability of crystallographic structures of SHMT from mesophilic organisms and information produced by the genomic projects prompted the analysis of the adaptation of SHMT to "extreme" environments, such as high temperatures, by exploitation of structural data from thermophilic organisms. The sequences of 10 thermophilic/hyperthermophilic SHMTs were multiply aligned to 53 mesophilic homologs and analyzed by a comparative approach, examining the amino acid compositions and preferred residue exchanges between mesophiles and extremophiles. The structural basis of the observed exchanges was further investigated through the application of homology modeling to the 10 extremophilic SHMTs. The results of this study indicate that, in SHMT, thermal stability can be achieved mainly through three strategies: (i) increased number of charged residues at the protein surface; (ii) increased hydrophobicity of the protein core; and (iii) substitution of thermolabile residues exposed to the solvent. Additional features of the archaeal SHMTs, for which no structural data are available yet, were also investigated to explain their quaternary assemblage and the interaction with modified folates.

Amino Acid Sequence↗

PubMed2003

Improvement in prediction of solvent accessibility by probability profiles.

The capability of predicting folding and conformation of a protein from its primary structure is probably one of the main goals of modern biology. An accurate prediction of solvent accessibility is an intermediate step along this way. A new method for predicting solvent accessibility from single sequence and multiple alignment data is described. The method is based on probability profiles calculated on an amino acid sequence centred on the residue whose accessibility has to be predicted. A profile is constructed for each exposure category considered so as to calculate the probability of a sequence being generated by the different profiles. Prediction accuracy was tested on a variety of protein sets with two- and three-state models. Different thresholds were used according to those adopted by the authors proposing the data sets. The prediction accuracy is significantly improved over existing methods.

Algorithms↗

PubMed2002

Comparative structural analysis of psychrophilic and meso- and thermophilic enzymes.

Enzymes adapted to cold display structures comparable with those of their meso- and thermophilic homologs but are characterized by a higher catalytic efficiency at low temperatures and by thermolability at moderate temperatures. To identify the structural factors responsible of such features, we undertook a systematic comparative analysis of several structural properties in a data set consisting of 7 cold active enzymes belonging to different structural families and 28 related structures from meso/thermophiles representing most of the structural information now available. Only high-resolution and high-quality structures were considered. Properties were calculated and then compared for each pair of 3D structures displaying different temperatures of adaptation using a temperature-weighting scheme. The significance of the resulting differences was evaluated with a statistical method. Results reveal that each protein family adopts different structural strategies to adapt to low temperatures. However, some common trends are observed: the number of ion pairs, the side-chain contribution to the exposed surface, and the apolar fraction of the buried surface show a consistent decrease with decreasing optimal temperatures.

Adaptation, Physiological↗