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Human (Hu) familial prion diseases are associated with about 40 point mutations of the gene coding for the prion protein (PrP). Most of the variants associated with these mutations are located in the globular domain of the protein. We performed 50 ns of molecular dynamics for each of these mutants to investigate their structure in aqueous solution. Overall,(More)
Ribosome-inactivating proteins (RIPs) are EC3.2.32.22 N-glycosidases that recognize a universally conserved stem-loop structure in 23S/25S/28S rRNA, depurinating a single adenine (A4324 in rat) and irreversibly blocking protein translation, leading finally to cell death of intoxicated mammalian cells. Ricin, the plant RIP prototype that comprises a(More)
Owing to the limited experimental resolution of data in macromolecular crystallography, ab initio phasing is successful only when atomic or quasi-atomic resolution data are available. It is shown that extrapolating the moduli and phases of non-measured reflections beyond and behind the experimental resolution limit makes the ab initio phasing process more(More)
Multidimensional heteronuclear nuclear magnetic resonance (NMR) spectroscopy provides valuable structural information about adducts between naturally unfolded proteins and their ligands. These are often highly pharmacologically relevant. Unfortunately, the determination of the contributions to observed chemical shifts changes upon ligand binding is(More)
The design and synthesis of a new class of nonpeptide direct thrombin inhibitors, built on the structure of 1-(pyridin-4-yl)piperidine-4-carboxamide, are described. Starting from a strongly basic 1-amidinopiperidine derivative (6) showing poor thrombin (fIIa) and factor Xa (fXa) inhibition activities, anti-fIIa activity and artificial membrane permeability(More)
Crystallography is a major tool for structure-driven drug design, as it allows knowledge of the 3D structure of protein targets and protein-ligand complexes. However, the route for crystal structure determination involves many steps, some of which may hamper its high-throughput use. Recent efforts have produced significant advances in experimental and(More)
Co-crystallization brings new opportunities for improving the solubility and dissolution rate of drugs with the chance of finely tuning some relevant chemical-physical properties of mixtures containing bioactive compounds. As co-crystallization process involves several molecular species, which are generally solid at room conditions, its control requires(More)
The intrinsic plasticity of protein residues, along with the occurrence of transitions between distinct residue conformations, plays a pivotal role in a variety of molecular recognition events in the cell. Analysis aimed at identifying both of these features has been limited so far to protein-complex structures. We present a computationally efficient tool(More)
A cationic soluble peroxidase isoenzyme (CysPrx) has been purified and characterized from artichoke (Cynara cardunculus subsp. scolymus (L.) Hegi) leaves by combination of aqueous two phase extraction, ion exchange chromatography, and gel filtration. The purification fold was 149 and the activity recovery 5.5%. CysPrx was stable from 5 to 45 °C with a pH(More)
An X-ray investigation has been performed with the aim of characterizing the binding sites of a platinum-based inhibitor (K[PtCl3(DMSO)]) of matrix metalloproteinase-3 (stromelysin-1). The platinum complex targets His224 in the S1' specificity loop, representing the first step in the selective inhibition process (PDB ID code 4JA1).