PubMed Journal Database | Biological chemistry 
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Showing PubMed Articles 1–25 of 76 from Biological chemistry
Progress in demystification of adhesion GPCR.
Abstract Adhesion G protein-coupled receptors (aGPCR) form the second largest class of GPCR. They are phylogenetically old and have been highly conserved during evolution. Mutations in representatives of this class are associated with severe diseases such as Usher Syndrome, a combined congenital deaf-blindness, or bifrontal parietal polymicrogyria. The main characteristics of aGPCR are their enormous size and the complexity of their N termini. They contain a highly conserved GPCR proteolytic site (GPS) and...
Abstract We have recently investigated the long-recognized relationship between complex I and group 4 [NiFe] hydrogenases and we have established the so-called Energy-converting hydrogenase related (Ehr) complex as a new member of the family. We have also observed that four subunits, homologues to NuoB, D, H and L, are common to the members of the family. We have designated this common group of subunits the universal adaptor. Taking into account the similarity of the Na+/H+ antiporter-like subunits of compl...
Galectins: new agonists of platelet activation.
Abstract Platelet activation at sites of vascular injury leads to the formation of a hemostatic plug and is crucial for hemostasis. However, uncontrolled platelet activation may lead to the formation of occlusive thrombi. Several soluble or matricellular proteins can activate platelets. In this article we review recent advances on the role of galectins in platelet physiology. Either in soluble or immobilized form, these endogenous glycan-binding proteins trigger platelet activation through modulation of dis...
Targeting caspases in cancer therapeutics.
Abstract The identification of the fundamental role of apoptosis in the growth balance and normal homeostasis against cell proliferation, led to the recognition of its loss contributing to tumorigenesis. The mechanistic significance of reinstating apoptosis signaling towards selective targeting of malignant cells heavily exploits the caspase family of death-inducing molecules as a powerful therapeutic platform for the development of potent anti-cancer strategies. Some apoptosis inhibitors induce caspase exp...
Abstract Cyclosporine A (CsA) is a cyclic undecapeptide, well known for its ability to prevent rejection episodes after organ transplantation via gain-of-function. Therefore, biomedical studies on CsA have been focused on both immunosuppressive properties and binding to the biocatalytically active immune receptors, the cyclophilins (Cyps). Much less attention has been spent on effects of cyclosporines on the biological function of other proteins. We used a 9-mer fluorescence-quenched peptide library with de...
Immunologically active peptides that accompany hen egg yolk IgY - separation and identification.
Abstract Protein mixture of cytokine-inducing activity accompanying chicken IgY, named yolkin, consists of several peptides of MW ranging from over 1 to 35 kDa. Yolkin and its constituent peptides were found to be efficient inducers of IL-1β, IL-6 and IL-10 secretion. N-terminal amino acid sequences of eight of the electrophoretically purified yolkin constituents revealed that all of them are homological to some fragments of the C-terminal domain of vitellogenin II. The fractions of MW about 4 and 12 kDa a...
A new trend in the Complex I research field.
Abstract To date, the 17th European Bioenergetics Conference (EBEC) in Freiburg, Germany (Sept. 15-20, 2012) was the most exciting conference for the complex I (NADH-Q oxidoreductase) research field. A whole day of oral presentations was dedicated to complex I, including 3 plenary lectures and 11 symposium talks. In addition, 43 posters were dedicated to complex I projects. This is a brief summary of an exciting paradigm shift from 'structure major' to 'structure + function', clearly observed in the complex...
Comparison of natural and recombinant tissue factor proteins: new insights.
Abstract Tissue factor (TF), an initiator of blood coagulation in vivo, is expressed in a variety of cells. Sufficient natural TF has been isolated to clone and express recombinant proteins ranging from full-length TF to its extracellular domain. Due to the limited availability of natural TF, recombinant proteins have been used as surrogates. Despite of the differences in their post-translational modifications, it has been accepted that membrane-anchored recombinant TFs are quite similar to the natural TF....
Abstract Asymmetric dimethylation of arginine side chains in proteins is a frequent post-translational modification, catalyzed by type I protein arginine methyltransferases (PRMTs). This article summarizes what is known about this modification in the nuclear poly(A) binding protein (PABPN1). PABPN1 contains thirteen dimethylated arginine residues in its C-terminal domain. Three enzymes, PRMT1, -3 and -6, can methylate PABPN1. Although 26 methyl groups are transferred to one PABPN1 molecule, the PRMTs do so...
Betulinic acid suppresses NGAL-induced epithelial-to-mesenchymal transition in melanoma.
Abstract Betulinic acid (BA) exhibits antitumoral activity by blocking proliferation, invasion, and angiogenesis. However, the impact of BA on epithelial-to-mesenchymal transition (EMT), a hallmark of cancer metastasis induced among others by neutrophil gelatinase-associated lipocalin (NGAL), remains unknown. The present study aimed at determining the effect of BA on NGAL-induced EMT. In A375 melanoma cells BA downregulated mesenchymal and increased epithelial markers, and inhibited cytoskeletal reorganizat...
Abstract Despite multiple advances in cancer therapies, glioblastoma (GBM) patients still have a poor prognosis. Numerous glioma models are used not only for the development of innovative therapies but also to optimize conventional ones. Given the significance of hypoxia in drug and radiation resistance and that hypoxia is widely observed among GBM, the establishment of a reliable method to map hypoxia in preclinical human models may contribute to the discovery and translation of future and more targeted th...
Structure of caa3-cytochrome c oxidase - a naturemade enzyme-substrate complex.
Abstract Aerobic respiration, the energetically most favorable metabolic reaction, depends on the action of terminal oxidases that include cytochrome c oxidases. The latter forms a part of the heme-copper oxidase superfamily and consists of three different families (A-, B- and C-types). The crystal structures of all families have now been determined, allowing a detailed structural comparison from evolutionary and functional perspectives. The A2-type oxidase, exemplified by the Thermus thermophilus caa3-oxid...
The Formate/Nitrite Transporter Family Of Anion Channels.
Abstract The Formate/Nitrite Transporter family of integral membrane proteins comprises pentameric channels for monovalent anions that exhibit a broad specificity for small anions such as chlo-ride, the physiological cargo molecules formate, nitrite and hydrosulfide, and also larger or-ganic acids. Three-dimensional structures are available for the three known subtypes, FocA, NirC, and HSC that reveal remarkable evolutionary optimizations for the respective physio-logical context of the channels. FNT channe...
The Regulation, Localization and Functions of Oxygen Sensing Prolyl Hydroxylase Phd3.
Abstract PHD3 prolyl 4-hydroxylase belongs to 2-oxoglutarate and iron-dependent dioxygenases. Together with the two closest paralogues, PHD1 and PHD2, these enzymes have been identified as cellular oxygen sensors that can mark the hypoxia-inducible factor-alpha (HIF-α) for pVHL-mediated proteasomal destruction. Although having overlapping functions with PHD1 and PHD2, PHD3 markedly differs from the two isoforms. PHD3 shows different expression pattern and subcellular localization as well as activity under...
ADAMTS: Novel Proteases Expressed by Activated Mast Cells.
Abstract Here we show that mast cells (MCs) express metalloproteases of the A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family, and that ADAMTS expression is influenced by MC activation. Co-culture of MCs with live Gram-positive bacteria caused a profound induction of ADAMTS-9 and -6, as well as downregulated expression of ADAMTS-5. Similar patterns were also seen after MC activation with calcium ionophore and by IgE receptor crosslinking. Moreover, ADAMTS-5, -6 and -9 were all i...
Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy.
Abstract Muscle loss during aging and disuse is a highly prevalent and disabling condition, but the knowledge about cellular pathways mediating muscle atrophy is still limited. Given the postmitotic nature of skeletal myocytes, the maintenance of cellular homeostasis relies on the efficiency of cellular quality control mechanisms. In this scenario, alterations in mitochondrial function are considered a major factor underlying sarcopenia and disuse muscle wasting. Damaged mitochondria not only are less bioen...
Abstract We hypothesized that kallikrein-related peptidase 4 (KLK14) is produced by colonic tumours and can promote tumourigenesis by activating proteinase-activated receptors (PARs). We found that: A) KLK14 is expressed in human colon adenocarcinoma cells but not in adjacent cancer-free tissue, B) KLK14 mRNA, present in colon cancer leads to KLK14 protein expression and secretion and that C) KLK14 signals via PAR-2 in HT-29 cells to cause: (1) receptor activation/internalization, (2) increases in intrace...
Dye selection for live cell imaging of intact siRNA.
Abstract Investigations into the fate of siRNA after transfection may unravel new ways to improve RNAi efficiency. Because intracellular degradation of RNA may prevent reliable observation of fluorescence labeled siRNA, new tools for fluorescence microscopy are warranted to cover the considerable duration of the RNAi effect. Here, the characterization and application of new FRET dye pairs for sensing the integrity of duplex siRNA is reported, that allow an assessment of the degradation status of an siRNA...
Oleic Acid is a Key Cytotoxic Component of HAMLET-like Complexes.
Abstract HAMLET is a complex of α-lactalbumin (α-LA) with oleic acid (OA) that selectively kills tumor cells and Streptococcus pneumoniae. To assess the contribution of the proteinaceous component to cytotoxicity of HAMLET, complexes of OA with proteins structurally and functionally distinct from α-LA were prepared. Similar to HAMLET, the OA complexes with bovine β-lactoglobulin (bLG) and pike parvalbumin (pPA) (bLG-OA-45 and pPA-OA-45) induced S. pneumoniae D39 cell death. The activation mechanisms o...
Abstract To exploit the B-lymphocyte antigen-CD20 binding capacity of the Ibritumomab tiuxetan (IBTN) monoclonal antibody (mAb) for imaging the over expression of B cell in non-Hodgkin's lymphoma (NHL) (a myeloproliferative disorder of the lymphatic system). In the current investigation we present the labeling of the IBTN with technetium-99m ((99m)Tc) through [(99m)Tc(CO)(3)](+) precursor for Radioimmunoimaging (RII) of the tumor prior to its treatment with (90)Y labeled IBTN. The labeled IBTN was radiob...
Polyglutamine Tracts as Modulators of Transcriptional Activation from Yeast to Mammals.
Abstract Microsatellite repeats are genetically unstable and subject to expansion and shrinkage. A subset of them, triplet repeats, can occur within the coding region and specify homomeric tracts of amino acids. Polyglutamine (polyQ) tracts are enriched in eukaryotic regulatory proteins, notably transcription factors, and we had shown before that they can contribute to transcriptional activation in mammalian cells. Here we generalize this finding by also including evolutionarily divergent organisms, namel...
Dimerization of human 5-lipoxygenase.
Abstract Human 5-lipoxygenase (5-LO) can form dimers as shown here via native gel electrophoresis, gel filtration chromatography and LILBID (laser induced liquid bead ion desorption) mass spectrometry. After glutathionylation of 5-LO by diamide/glutathione treatment, dimeric 5-LO was no longer detectable and 5-LO almost exclusively exists in the monomeric form which showed full catalytic activity. Incubation of 5-LO with diamide alone led to a disulfide-bridged dimer and to oligomer formation which displa...
Squalene monooxygenase - a target for hypercholesterolemic therapy.
Abstract Squalene monooxygenase catalyzes the epoxidation of C-C double bond of squalene to yield 2,3-oxidosqualene, the key step of sterol biosynthesis pathways in Eukaryotes. Sterols are essential compounds of these organisms and squalene epoxidation is an important regularory point in their synthesis. Squalene monooxygenase down regulation in vertebras and fungi decreases synthesis of cholesterol and ergosterol, respectively, which makes squalene monooxygenase the potent and attractive target of hyperc...
Identification of ATF2 as a transcriptional regulator of renin gene.
Abstract The cAMP response element (enhCRE) in the distal enhancer regulatory region of renin gene is believed to play major role in the control of renin transcription. enhCRE binds the CRE-binding protein (CREB), which is the main transcription factor target of cAMP signaling. Using the mouse renin-producing cell line As4.1 we find now that activating transcription factor-2 (ATF2) also binds to enhCRE. N-terminal phosphorylation of ATF2, which controls its transactivation, associated with downregulation...
Abstract Matrix metalloproteinases cleave and degrade most components of the extracellular matrix and unregulated MMP activity has been correlated to cancer and metastasis. Hence there is a burgeoning need to develop inhibitors that bind selectively to structurally similar MMPs. The inhibition profiles of peptidomimetics containing Cαsubstituents at the α,βunsaturated carbon were evaluated against the recombinant forms of ADAM17, MMP1 and -9. The dicarboxylic acid D2 and hydroxamate C2 inhibited MMP9 but...
