Descripción: The title complex, aqua(2,2′-bipyridy-N,N′(3-thiapentanedioate-O,S,O′)zinc(II) tetrahydrate, [Zn(C4H4-O4S)(C10H8N 2)(H2O)].4H2O, is mononuclear with a coordination sphere consisting of one S, two N and three O atoms. The Zn atom is linked to a tridentate thiodiacetate ligand, a bidentate 2,2′-bipyridine ligand and an aqua ligand resulting in a slightly distorted octahedral coordination geometry. The molecular units are linked together in the crystal by an extensive hydrogen-bonding network and by intermolecular S⋯S interactions.

Descripción: A new polymeric phase of zinc(II) oxydiacetate, catena-poly[[[diaquazinc(II)]-μ-oxydiacetato] hydrate], {[Zn(C4H4-O5)(H2O)2] ·H2O}n, isomorphous with the Co homologue [Hatfield, Helms, Rohrs, Singh, Wasson & Weller (1987). Proc. Indian Acad. Sci. Chem. Sci. 98, 23-31], is reported. It presents a chain-like structure, generated by ZnO6 cores which are bridged by carboxylate groups in an anti-anti conformation along the unique crystallographic b axis. The chains are held together through hydrogen-bonding interactions with the three water molecules.

Descripción: The three transition-metal complexes, (meso-5,7,7,12,14,14-hexa methyl-1,4,8,11-tetra azacyclo tetra decane-κ4 N)bis (perchlorato-κO)copper(II), [Cu(ClO4)2(C18H40N4)], (I), (meso-5,7,7,12,14,14-hexa methyl-1,4,8,11-tetra azacyclo tetra decane-κ4 N)bis (nitrato-κO)zinc(II), [Zn(NO3)2(C18H40N4)], (II), and aqua chlorido (meso-5,7,7,12,14,14-hexa methyl-1,4,8,11-tetraazacyclo tetra decane-κ4 N)copper(II) chloride, [CuCl(C18H40N4)(H2O)]Cl, (III), are described. The mol ecules display a very similarly distorted 4+2 octa hedral environment for the cation [located at an inversion centre in (I) and (II)], defined by the macrocycle N4 group in the equatorial sites and two further ligands in trans-axial positions [two O-ClO3 ligands in (I), two O-NO2 ligands in (II) and one chloride and one aqua ligand in (III)]. The most significant difference in mol ecular shape resides in these axial ligands, the effect of which on the intra- and inter molecular hydrogen bonding is discussed. In the case of (I), all strong hydrogen-bond donors are saturated in intra molecular inter actions, while weak inter molecular C - H⋯O contacts result in a three-dimensional network. In (II) and (III), instead, there are N - H and O - H donors left over for inter molecular inter actions, giving rise to the formation of strongly linked but weakly inter acting chains. © 2013 International Union of Crystallography.

Descripción: In the present work, we have used the papillomavirus E7 oncoprotein to pursue structure-function and evolutionary studies that take into account intrinsic disorder and the conformational diversity of globular domains. The intrinsically disordered (E7N) and globular (E7C) domains of E7 show similar degrees of conservation and co-evolution. We found that E7N can be described in terms of conserved and coevolving linear motifs separated by variable linkers, while sequence evolution of E7C is compatible with the known homodimeric structure yet suggests other activities for the domain. Within E7N, inter-residue relationships such as residue co-evolution and restricted intermotif distances map functional coupling and co-occurrence of linear motifs that evolve in a coordinate manner. Within E7C, additional cysteine residues proximal to the zinc-binding site may allow redox regulation of E7 function. Moreover, we describe a conserved binding site for disordered domains on the surface of E7C and suggest a putative target linear motif. Both homodimerization and peptide binding activities of E7C are also present in the distantly related host PHD domains, showing that these two proteins share not only structural homology but also functional similarities, and strengthening the view that they evolved from a common ancestor. Finally, we integrate the multiple activities and conformations of E7 into a hierarchy of structure-function relationships. © 2012 Chemes et al.

Descripción: Background: Self-assembly is a common theme in proteins of unrelated sequences or functions. The human papillomavirus E7 oncoprotein is an extended dimer with an intrinsically disordered domain, that can form large spherical oligomers. These are the major species in the cytosol of HPV transformed and cancerous cells. E7 binds to a large number of targets, some of which lead to cell transformation. Thus, the assembly process not only is of biological relevance, but represents a model system to investigate a widely distributed mechanism. Methodology/Principal Findings: Using various techniques, we monitored changes in secondary, tertiary and quaternary structure in a time course manner. By applying a robust kinetic model developed by Zlotnik, we determined the slow formation of a monomeric "Z-nucleus" after zinc removal, followed by an elongation phase consisting of sequential second-order events whereby one monomer is added at a time. This elongation process takes place at a strikingly slow overall average rate of one monomer added every 28 seconds at 20 μM protein concentration, strongly suggesting either a rearrangement of the growing complex after binding of each monomer or the existence of a "conformation editing" mechanism through which the monomer binds and releases until the appropriate conformation is adopted. The oligomerization determinant lies within its small 5 kDa C-terminal globular domain and, remarkably, the E7 N-terminal intrinsically disordered domain stabilizes the oligomer, preventing an insoluble amyloid route. Conclusion: We described a controlled ordered mechanism with features in common with soluble amyloid precursors, chaperones, and other spherical oligomers, thus sharing determining factors for symmetry, size and shape. In addition, such a controlled and discrete polymerization reaction provides a valuable tool for nanotechnological applications. Finally, its increased immunogenicity related to its supramolecular structure is the basis for the development of a promising therapeutic vaccine candidate for treating HPV cancerous lesions. © 2012 Smal et al.

Descripción: 1. 1. The effect of several metals and reagents on the decarboxylation rate of uroporphyrinogen I by using a 16-fold purified preparation of Uroporphyrinogen Decarboxylase from Rhodopseudomonas palustris, was studied. 2. 2. 1 mM Hg2+ and Cu2+ were strong inhibitors, 1 mM Zn2+ and Fe2+ under certain conditions and 1 mM Fe3+ and Cr3+ also inactivated the enzyme, but Pb2+, Cd2+, and Al3+ did not. Metals inhibition was reversed by 1 mM GSH or CvSH. 3. 3. 0.1 mM DTNB and PCMB, 1 mM pyridoxal phosphate and 100 mM chloral hydrate, as well as 1 mM 2-methoxy-5-nitrotropone and 0.2 mM diethylpyrocarbonate inhibited Uroporphyrinogen Decarboxylase; while GSH, CySH, N-ethylmaleimide, sodium thioglycolate, 1,4-dithioerythritol, EDTA and O-phenantroline did not modify activity. 4. 4. Data obtained would indicate that one cysteine, one or two histidine residues and probably a lysine group are required for enzyme activity. © 1987.

Descripción: We present stopping power measurements of Zn for C and O ions and compare them with a theoretical description given by the Transport Cross Section - Extended Friedel Sum Rule (TCS-EFSR) for the valence electrons, and two different models for the inner-shells: the Shellwise Local Plasma Approximation (SLPA) and the CasP approach. The SLPA, which successfully applies to projectiles from H to B, is slightly high for C ions and clearly overestimates the data for O ions. On the other hand, total stopping results using the CasP description for the inner-shells show good agreement with the data for C and O ions, and also with the SRIM predictions. © Published under licence by IOP Publishing Ltd.

Descripción: Background: Alzheimer's disease (AD) is characterized by a neurodegenerative progression that alters cognition. On a phenotypical level, cognition is evaluated by means of the MiniMental State Examination (MMSE) and the post-morten examination of Neurofibrillary Tangle count (NFT) helps to confirm an AD diagnostic. The MMSE evaluates different aspects of cognition including orientation, short-term memory (retention and recall), attention and language. As there is a normal cognitive decline with aging, and death is the final state on which NFT can be counted, the identification of brain gene expression biomarkers from these phenotypical measures has been elusive. Methodology/Principal Findings: We have reanalysed a microarray dataset contributed in 2004 by Blalock et al. of 31 samples corresponding to hippocampus gene expression from 22 AD subjects of varying degree of severity and 9 controls. Instead of only relying on correlations of gene expression with the associated MMSE and NFT measures, and by using modern bioinformatics methods based on information theory and combinatorial optimization, we uncovered a 1,372-probe gene expression signature that presents a high-consensus with established markers of progression in AD. The signature reveals alterations in calcium, insulin, phosphatidylinositol and wnt-signalling. Among the most correlated gene probes with AD severity we found those linked to synaptic function, neurofilament bundle assembly and neuronal plasticity. Conclusions/Significance: A transcription factors analysis of 1,372-probe signature reveals significant associations with the EGR/KROX family of proteins, MAZ, and E2F1. The gene homologous of EGR1, zif268, Egr-1 or Zenk, together with other members of the EGR family, are consolidating a key role in the neuronal plasticity in the brain. These results indicate a degree of commonality between putative genes involved in AD and prion-induced neurodegenerative processes that warrants further investigation. © 2010 Go ́mez Ravetti et al.

Descripción: The isomorphous title compounds, [Tr(S4O6)(C 12H12N2)2]·2C 3H7NO (Tr = CdII and ZnII), consist of metal centres to which one tetrathionate and two 4,4′-dimethyl-2, 2′-bipyridine chelating ligands bind. The structures are completed by two symmetry-related dimethylformamide solvent molecules. Each metal-centred complex is bisected by a twofold axis running through the metal centre and halving the chelating tetrathionate dianion through the central S - S bond. The ancillary symmetry-related 4,4′-dimethyl-2,2′-bipyridine ligands act as chelates. This results in a distorted six-coordinate geometry, with similar Tr - O/N distances but central angles differing substantially from 90 and 180°. Both ligands are basically featureless from a geometric point of view, with torsion angles in both coordinated tetrathionate groups suggesting a trend linking metal size (covalent radius) and ligand 'openness'. Packing is directed by (C - H)aromatic⋯O bridges and π-π offset stacked interactions defining chains along [001], further linked by weaker (C - H)methyl⋯O bridges, some of them mediated by the dimethylformamide solvent molecules. © 2013 International Union of Crystallography.

Descripción: Oxidative stress plays a critical role in the pathogenesis of diabetes, hypertension and atherosclerosis. Some authors reported that fat accumulation correlates to systemic oxidative stress in humans and mice, but the relationship of lipid production and oxidative metabolism is still unclear. In our laboratory we used 3T3-L1 preadipocytes, which are able to differentiate into mature adipocytes and accumulate lipids, as obesity model. We showed that intracellular reactive oxygen species (ROS) and antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities increased in parallel with fat accumulation. Meanwhile N-acetylcysteine (NAC), a well known antioxidant and Glutathione (GSH) precursor, inhibited ROS levels as well as fat accumulation in a concentration-dependent manner. NAC also inhibited both adipogenic transcription factors CCAAT/enhancer binding protein beta (C/EBP) and peroxisomal proliferator activated receptor gamma (PPAR β) expression; we suggested that intracellular GSH content could be responsible for these effects. © 2011 by the authors; licensee MDPI, Basel, Switzerland.