837 research outputs found
Crystal structure of archeal protoglobin: Novel ligand diffusion paths to the heme
No full textThe protein structural adaptability of the globin fold has been highlighted by the recent discovery of 2-on-2 hemoglobins, of neuroglobin, cytoglobin, and the characterization of their three-dimensional structures. Protoglobin from Methanosarcina acetivorans C2A is the latest entry in the hemoglobin superfamily, adding to it new structural variability and functional complexity. The 1.3˚A crystal structure of oxygenated M. acetivorans protoglobin shows that, contrary to all known globins, protoglobin-specific loops and a N-terminal extension completely bury the heme within the protein matrix. Access of diatomic ligands (such as O2, CO, and NO) to the heme is however granted by protoglobin-specific apolar tunnels that reach the heme distal site from entry sites at the B/G and B/E helix interfaces. Functionally, M. acetivorans dimeric protoglobin displays a selectivity ratio for O2/CO binding to the heme that favours O2 ligation, a property that is
exceptional within the hemoglobin superfamily
Entrevista a Giovanni Pesce
No full textL�autor ens presenta l�entrevista a Giovanni Pesce, antic vetear italià que participà a la Guerra
d�Espanya amb les Brigades InternacionalsThe author shows in this paper the interview with Giovanni Pesce, old italian veteran that fought in the
Spanish Civil War as a member of the International Brigade
Entrevista a Giovanni Pesce
No full textL’autor ens presenta l’entrevista a Giovanni Pesce, antic vetear italià que participà a la Guerra d’Espanya amb les Brigades Internacionals.The author shows in this paper the interview with Giovanni Pesce, old italian veteran that fought in the Spanish Civil War as a member of the International Brigades
Come ci ha insegnato Guido Fink?
No full textLa cultura americana attraverso i film, shakespeare e il cinema, Henry James e il cinem
Truncated (2/2) hemoglobin : Unconventional structures and functional roles in vivo and in human pathogenesis
No full textTruncated hemoglobins (trHbs) build a sub-class of the globin family, found in eubacteria, cyanobacteria, unicellular eukaryotes, and in higher plants; among these, selected human pathogens are found. The trHb fold is based on a 2/2 alpha-helical sandwich, consisting of a simplified and reduced-size version of the classical 3/3 alpha-helical sandwich of vertebrate and invertebrate globins. Phylogenetic analysis indicates that trHbs further branch into three groups: group I (or trHbN), group II (or trHbO), and group III (or trHbP), each group being characterized by specific structural features. Among these, a protein matrix tunnel, or a cavity system implicated in diatomic ligand diffusion through the protein matrix, is typical of group I and group II, respectively. In general, a highly intertwined network of hydrogen bonds stabilizes the heme bound ligand, despite variability of the heme distal residues in the different trHb groups. Notably, some organisms display genes from more than one trHb group, suggesting that trHbN, trHbO, and trHbP may support different functions in vivo, such as detoxification of reactive nitrogen and oxygen species, respiration, oxygen storage/sensoring, thus aiding survival of an invading microorganism. Here, structural features and proposed functions of trHbs from human pathogens are reviewed
Caratterizzazione molecolare dei prodotti ittici (pesce ghiaccio) di importazione cinese ai fini della tutela del consumatore
No full textCaratterizzazione molecolare dei prodotti ittici, in particolare il pesce ghiaccio, di importazione cinese
Protein structure in the truncated (2/2) hemoglobin family
No full textProtein matrix cavities and extended tunnels can effectively channel substrates and products to and from active sites in enzymes. Substrate and product channeling can enhance catalytic efficiency by reducing the intramolecular diffusion times to and from reaction centers. Moreover, protected transfer between sites may prevent the release of reactive intermediates, thus promoting efficiency or regulation in a series of interconnected reactions. This overview concerns the characterization of matrix tunnels in 2/2 hemoglobins, the recently described family of small hemoproteins (found in bacteria, plants, and unicellular eukaryotes) that form a separate cluster within the hemoglobin superfamily. Crystallographic investigations have shown that the 2/2 hemoglobin fold (a 2-on-2 alpha-helical sandwich) hosts a protein matrix tunnel system offering a potential path for ligand diffusion to and from the heme distal site. The tunnel topology is conserved in 2/2 hemoglobin group I, although with modulation of its size and/or structure. This article describes the methods that were adopted to characterize such matrix tunnels through analysis of the crystal structures and through binding of small apolar ligands to crystalline 2/2 hemoglobins. The methods are generally applicable and, in the case of 2/2 hemoglobins, underline the potential role of the tunnel system in supporting ligand diffusion to and from the heme, as well as ligand storage within the protein matrix
Protein fold and structure in the truncated (2/2) globin family
No full textAnalysis of amino acids sequences and protein folds has recently unraveled the structural bases and details of several proteins from the recently discovered "truncated hemoglobin" family. The analysis here presented, in agreement with previous surveys, shows that truncated hemoglobins can be classified in three main groups, based on their structural properties. Crystallographic analyses have shown that all three groups adopt a 2-on-2 alpha-helical sandwich fold, resulting from apparent editing of the classical 3-on-3 alpha-helical sandwich of vertebrate and invertebrate conventional globins. Specific structural features distinguish each of the three groups. Among these, a protein matrix tunnel system is typical of group I, a Trp residue at the G8 topological site is conserved in groups II and III, and TyrB10 is almost invariant through the three groups. A strongly intertwined network of hydrogen bonds stabilizes the heme bound ligand, despite variability of the heme distal residues observed in the different proteins considered. Details of ligand recognition in the three groups are discussed at the light of residue conservation and of differing ligand diffusion pathways to the heme. Based on structural analyses of the family-specific fold, we endorse a recent proposal of leaving the "truncated hemoglobins" term, that does not represent properly the observed 2-on-2 alpha-helical sandwich fold, and adopting the simple "2/2Hb" term to concisely address this protein family
Synthesis and biological evaluation of thiazole derivatives on basic defects underlying cystic fibrosis.
No full textCystic fibrosis is a genetic disease caused by loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator gene, encoding for CFTR protein. The most frequent mutation is the deletion of phenylalanine at position 508 (F508del), which leads to distinct defects in channel gating and cellular processing. In last years, several thiazole containing small molecules, endowed with dual F508del-CFTR modulator activity, proved to be able to target these defects. In search of new chemical entities able to restore CFTR function, we designed and synthesized a small series of sixteen thiazole derivatives. The designed compounds were studied as correctors and potentiators of F508del-CFTR. Although none of the molecules showed significant corrector activity, compounds 10 and 11 exhibited potentiator effects, thus allowing to determine some basic structural features which enable to obtain F508del-CFTR potentiator activity. In silico ADME studies showed that these derivatives obey Lipinski’s rule of five and are expected to be orally bioavailable. Therefore, these molecules may represent a good starting point for the design of analogues endowed with improved CFTR potentiator activity and a good pharmacokinetic profile
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