1,721,020 research outputs found
Combined X-ray crystallographic, in situ UV-Vis and QM/MM studies highlight alternate retinal binding modes in CRALBP
No full textHomeostasis of α-Tocopherol and of 11-cis-Retinal is Regulated by Proteins of the Sec14 Superfamily
No full textCRALBP as well as a-TTP are members of the SEC14 like family of lipid carriers. There are about 30 SEC14 like genes in the the human genome. We are interested in the structural and functional elucidation of this class of proteins. SEC14like proteins have coevolved with eukaryotic organisms and are involved in the transport and the secretion of specific lipid molecules such as Vitamin A and Vitamin E. A common theme of SEC14 like functions is to prevent the accumulation of lipids at toxic levels in the cellular context
Tocopherol-binding proteins: their function and physiological significance.
No full textThe present review is a continuation of earlier essays on the uptake mechanisms and the biological function of vitamin E. There are eight naturally occurring homologues of vitamin E, which differ in their structure and in biological activity in vivo and in vitro. Various studies have suggested that after normal gastrointestinal absorption of dietary vitamin E specific mechanisms favor the preferential accumulation of one of its homologues, alpha-tocopherol, in the human body. This process is thought to be mediated in part by the alpha-tocopherol transfer protein (alpha-TTP) in the liver cytoplasm. The mechanism and pathway by which alpha-TTP specifically incorporates alpha-tocopherol into plasma lipoproteins is not yet fully understood. Because alpha-tocopherol is widely distributed in tissues in various concentrations but alpha-TTP resides only in liver, its role as intracellular carrier of alpha-tocopherol seems unlikely. However, recent data indicate that a system of alpha-tocopherol-binding proteins is involved in these processes that favor the localization of alpha-tocopherol at the sites where it is required. The current status of the evidence for the regulation of alpha-tocopherol levels and their impact on cellular signaling is discussed
Molecular mechanisms of vitamin E transport.
No full textVitamin E is the most important lipid-soluble antioxidant in humans. Specific tocopherol-binding proteins favor the retention of the most potent vitamin E homologue, RRR-alpha-tocopherol (RRR-alpha-T) in man. The crystal structures of both the ligand-charged and the apo-forms of human alpha-tocopherol transfer protein (alpha-TTP) and of human supernatant protein factor (SPF) have been solved. The renewed interest in the biological function of tocopherol binders is based on the discovery of ataxia with vitamin E deficiency, a neurological disorder that is caused by genetic defects of the alpha-TTP gene and/or vitamin E deficiency. The analysis of the crystal structure of alpha-TTP provides the molecular basis of vitamin E retention in man. SPF has been reported to enhance cholesterol biosynthesis by facilitating the conversion of squalene to lanosterol. Nevertheless, the physiological role of SPF as well as its ligand specificity is not known. Investigations on the substrate specificity of SPF have uncovered binding of RRR-alpha-tocopherylquinone (RRR-alpha-TQ). RRR-alpha-TQ represents the major physiological oxidation product of RRR-alpha-T. The three-dimensional overlay of the ligand-charged structures of SPF and alpha-TTP indicates that ligand specificity in both proteins is mostly modulated by side-chain variations rather than by the backbone. Recent reports point towards the in vivo reduction of RRR-alpha-TQ to RRR-alpha-TQH(2) and its protective role in low-density lipoprotein oxidation. On the basis of these reports, it is proposed that SPF may enhance cholesterol biosynthesis indirectly by mediating the transfer of RRR-alpha-TQ to low-density lipoprotein, thus reducing oxidation of low-density lipoprotein and its subsequent cellular uptake by scavenger receptors
Supernatant protein factor in complex with RRR-alpha-tocopherylquinone: a link between oxidized Vitamin E and cholesterol biosynthesis.
No full textThe vast majority of monomeric lipid transport in nature is performed by lipid-specific protein carriers. This class of proteins can enclose cognate lipid molecules in a hydrophobic cavity and transport them across the aqueous environment. Supernatant protein factor (SPF) is an enigmatic representative of monomeric lipid transporters belonging to the SEC14 family. SPF stimulates squalene epoxidation, a downstream step of the cholesterol biosynthetic pathway, by an unknown mechanism. Here, we present the three-dimensional crystal structure of human SPF in complex with RRR-alpha-tocopherylquinone, the major physiological oxidation product of RRR-alpha-tocopherol, at a resolution of 1.95A. The structure of the complex reveals how SPF sequesters RRR-alpha-tocopherylquinone (RRR-alpha-TQ) in its protein body and permits a comparison with the recently solved structure of human alpha-tocopherol transfer protein (alpha-TTP) in complex with RRR-alpha-tocopherol. Recent findings have shown that RRR-alpha-TQ is reduced in vivo to RRR-alpha-TQH(2), the latter has been suggested to protect low-density lipoprotein (LDL) particles from oxidation. Hence, the antioxidant function of the redox couple RRR-alpha-TQ/RRR-alpha-TQH(2) in blocking LDL oxidation may reduce cellular cholesterol uptake and thus explain how SPF upregulates cholesterol synthesis
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
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Identification of The Tocopherol-Cyclase in the Blue-Green Algae Anabaena variabilis KÜTZING (Cyanobacteria)
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