Abstract: Missing

Abstract: La differenza piu' drammatica tra oppioidi derivati dalle piante e peptidi oppioidi e' l'inversione di chiralita' del carbonio alfa della unita' tiramminica comune alle due classi di composti. Questa inversione e' tanto piu' sorprendente se si considera che il composto di partenza nella biosintesi degli alcaloidi dell'oppio e' pur sempre la L-tirosina, cioe' il primo residuo di tutti i peptidi oppioidi. Noi ipotizziamo che la presenza di Gly2 o D-Ala2 nei due piu' comuni domini messaggio degli oppioidi (YGGF e YaF) serva a compensare l'inversione di chiralita', consentendo l'accessibilita' di conformazioni non canoniche. Una scansione pressoche' completa dello spazio conformazionale accessibile a Tyr-D-Ala-Phe-NH-CH3 e al suo isomero Tyr-L-Ala-Phe-NH-CH3 conferma questa ipotesi e contribuisce a stabilire un solido collegamento tra oppioidi alcaloidici e peptidici. Questo risultato rafforza la convinzione che la morfina, come altri composti neurologicamente attivi presenti nelle piante, possa legarsi, nelle piante, a recettori endogeni preposti a sistemi di comunicazione cellulare. Un "sottoprodotto" non banale dell'analisi conformazionale e' una conformazione bioattiva per peptidi contenenti il messaggio YaF molto piu' attendibile di quelle derivate da studi di tipo SAR.

Abstract: The homology modelling of the structures of the 162 type II modules from the giant multi-domain protein titin is reported. The package Modeller was used and implemented in an automated fashion using four experimentally solved structures as templates. Validation of the models was addressed in terms of divergence from the template and consensus of the alignments. The homology within the whole family of type II modules as well as with the templates is relatively high (30-40% identity and ca. 60% similarity). Comparison between the models of domains for which an NMR structure has been solved with the experimental solution gives an estimate of the quality. Our results allow us to distinguish a number or structurally relevant residues that are therefore conserved in the whole family and buried in the hydrophobic core from those residues that are exposed and conserved. These will be funtionally relevant. Comparison of exposed conserved patches for modules in different regions of the titin molecule suggests potential interaction surfaces. Our results may be tested directly for those modules whose binding partner is known.

Abstract: Protein structure determination by NMR spectroscopy has become an essential tool in biological laboratories and so new methods are necessary, to perform 3D-structure determinations automatically. In view of the larger number of sequences becoming available, for example, from genome projects, the structural determination on a large scale is required, which could not be carried out without a high degree of automation. One of the most time-consuming steps in protein structure determination is the spectral assignment procedure. This involves two main phases: a) sequence specific resonance assignment of the nmr signals; b) assignment of the NOESY spectra with collection of a list of distance constraints: the crucial step. Advanced iterative approaches have been suggested to automate the assignment of NOESY spectra and 3D-structure calculation. We suggest an approach that simulates "molecular replacement methods" now currently in use in crystallography. A structure, obtained for instance from homology modelling or x-ray coordinates, may be used as template to automatically provide an initial guess. This structure can be then routinely refined against the experimental NMR data. We have applied this approach to determine the structure of Phl p II allergen, a protein of 96 residues with an immunoglobulin-like fold, of which both nmr and x-ray structures were available.

Abstract: Missing