1,721,129 research outputs found
Determination of the dihedral angle ψ based on J coupling measurements in 15N/13C-labeled proteins
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Hemoprotein models based on a covalent helix-heme-helix sandwich - 4. Discrimination of paramagnetic Fe(III)-mimochrome I Delta and Lambda isomers by NMR spectroscopy
No full textA 1H NMR study of the paramagnetic Fe(III)-Mimochrome I, a porphyrin peptide compound based on a covalent helix-porphyrin-helix sandwich, prototype of a new class of heme-protein models, is reported. The study demonstrates that Fe(III)-Mimochrome I exists, in d7-DMF solution at millimolar concentration, as two hexacoordinated Δ and Λ isomers. It represents the first observation of two isomeric forms of a bis-histidine Fe(III)-porphyrin peptide adduct. 1H NMR studies in d7-DMF solution of the paramagnetic Fe(III) deuteroporphyrin dimethylester (DPDME), either as acetate (Ac) or chloride salts, are also reported for comparison. In the acetate form this compound gives detectable different mixed-ligand isomers by imidazole addition, while the chloride form gives preferentially the bis-imidazole complex. © 1998 Elsevier Science S.A. All rights reserved
SODIUM BUMETANIDE TRIHYDRATE
No full textThe structure of sodium 3-(aminosulfonyl)-5-(butyl-amino)-4-phenoxybenzoate trihydrate (sodium bumetanide trihydrate), Na +.C 17H19N2O5S-.3H2O, consists of a layer of sodium ions and water molecules between two layers of bumetanide molecules. Six-coordinate Na+ ions linked by water molecules are arranged in columns parallel to b
Discovery of a novel class of reversible non-peptide caspase inhibitors via a structure-based approach
No full textIn this paper, we report a simple structure-based iterative optimizations (SUBITO) strategy to identify and optimize new protein ligands and inhibitors. The approach is based on a combination of NMR-based screening and computational docking methods and enabled the identification of novel chemical leads among hundreds of thousands of commercially available compounds by screening only a few hundred compounds from a scaffold library followed by iterative screening steps where only few dozen compounds are tested. As an application, we report on the discovery of a novel class of non-peptide reversible caspase inhibitors, with IC50 values in the low micromolar range. © 2005 American Chemical Society
Targeting Zinc Finger Domains with Small Molecules: Solution Structure and Binding Studies of the RanBP2-Type Zinc Finger of RBM5
No full textThe RNA binding motif protein 5 (RBM5), also known as Luca15 or H37, is a component of prespliceosomal complexes that regulates the alternative splicing of several mRNAs, such as Fas and caspase-2. The RBM5 gene is located at the 2p21.3 chromosomal region, which is strongly associated with lung cancer and many other cancers. Both increased and decreased levels of RBM5 can play a role in tumor progression. In particular, downregulation of rbm5 is involved in lung cancer and other cancers upon Ras activation, and, also, represents a molecular signature associated with metastasis in various solid tumors. On the other hand, upregulation of RBM5 occurs in breast and ovarian cancer. Moreover, RBM5 was also found to be involved in the early stage of the HIV-1 viral cycle, representing a potential target for the treatment of the HIV-1 infection. While the molecular basis for RNA recognition and ubiquitin interaction has been structurally characterized, small molecules binding this zinc finger (ZF) domain that might contribute to characterizing their activity and to the development of potential therapeutic agents have not yet been reported. Using an NMR screening of a fragment library we identified several binders and the complex of the most promising one, compound 1, with the RBM5 ZF1 was structurally characterized in solution. Interestingly, the binding mechanism reveals that 1 occupies the RNA binding pocket and is therefore able to compete with the RNA to bind RBM5 RanBP2-type ZF domain, as indicated by NMR studies. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Structural and functional studies of Stf76 from the Sulfolobus islandicus plasmid-virus pSSVx: A novel peculiar member of the winged helix-turn-helix transcription factor family
No full textThe hybrid plasmid-virus pSSVx from Sulfolobus islandicus presents an open reading frame encoding a 76 amino acid protein, namely Stf76, that does not show significant sequence homology with any protein with known 3D structure. The recombinant protein recognizes specifically two DNA-binding sites located in its own promoter, thus suggesting an auto-regulated role of its expression. Circular dichroism, spectrofluorimetric, light scattering and isothermal titration calorimetry experiments indicated a 2:1 molar ratio (protein:DNA) upon binding to the DNA target containing a single site. Furthermore, the solution structure of Stf76, determined by nuclear magnetic resonance (NMR) using chemical shift Rosetta software, has shown that the protein assumes a winged helix-turn-helix fold. NMR chemical shift perturbation analysis has been performed for the identification of the residues responsible for DNA interaction. In addition, a model of the Stf76-DNA complex has been built using as template a structurally related homolog. © 2014 The Author(s) 2014
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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