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Biological Chemistry

Leszek Szablewski, Anna Sulima
It is known fact that diabetes mellitus (DM) affects blood cells. Changes in the erythrocyte membrane, disorder in hemoglobin oxygen-binding and modification in mechanical characteristics, are effects of hyperglycemia on red blood cells. Altered susceptibility infection of patients with diabetes has been ascribed to a depression in the function of polymorphonuclear leukocytes. Neutrophil function in case of patients with diabetes with good glucose control is slightly different than in the case of healthy ones...
October 21, 2016: Biological Chemistry
Vito Iacobazzi, Vittoria Infantino, Alessandra Castegna, Alessio Menga, Erika Mariana Palmieri, Paolo Convertini, Ferdinando Palmieri
Significant metabolic changes occur in the shift from resting to activated cellular status in inflammation. Thus, changes in expression of a large number of genes and extensive metabolic reprogramming gives rise to acquisition of new functions (e.g. production of cytokines, intermediates for biosynthesis, lipid mediators, PGE, ROS and NO). In this context, mitochondrial carriers, which catalyze the transport of solute across mitochondrial membrane, change their expression to transport mitochondrially produced molecules, among which citrate and succinate, to be used as intracellular signalling molecules in inflammation...
October 11, 2016: Biological Chemistry
Thomas Marcellino, Vasundara Srinivasan
ABC exporters are highly dynamic membrane proteins that span a huge spectrum of different conformations. A detail integrated approach of cellular, biochemical and biophysical characterization of these 'open', 'closed' and other intermediate states is central to understanding their function. Almost 40 years after the discovery of the first ABC transporter, thanks to the enormous development in methodologies, a picture is slowly emerging to visualize how these fascinating molecules transport their substrates...
October 11, 2016: Biological Chemistry
Judith Clements
No abstract text is available yet for this article.
October 6, 2016: Biological Chemistry
Zela Keuylian, Alain Hovnanian
Protease regulation plays a crucial role in skin homeostasis and inflammation as revealed by the identification of loss-of-function mutations in SPINK5 (serine protease inhibitor of Kazal type 5) in Netherton sydrome (NS). SPINK5 encodes LEKTI (lympho-epithelial Kazal type related inhibitor), a multi-domain serine protease inhibitor expressed in all stratified epithelia. Our laboratory has developed a number of murine models which have been instrumental to dissecting the pathogenesis of NS. This mini-review discusses the major findings of these models and emphasizes the role of protease regulation, especially Kallikrein related peptidases in NS...
October 6, 2016: Biological Chemistry
Stefanie J Kellermann, Andrea Rentmeister
Sequence-specific and programmable binding of proteins to RNA bears potential to detect and manipulate target RNAs. Applications include analysis of subcellular RNA localization or post-transcriptional regulation but require sequence-specificity to be readily adjustable to any target RNA. The Pumilio homology domain binds an eight nucleotide target sequence in a predictable manner allowing for rational design of variants with new specificities. We describe a high-throughput system for screening Pumilio variants based on fluorescenceactivated cell sorting of E...
September 28, 2016: Biological Chemistry
Sara Fernández-Lizarbe, Emilio Lecona, Angélica Santiago-Gómez, Nieves Olmo, M Antonia Lizarbe, Javier Turnay
Annexin A13 is the founder member of the vertebrate family of annexins, which are comprised of a tetrad of unique conserved domains responsible for calcium-dependent binding to membranes. Its expression is restricted to epithelial intestinal and kidney cells. Alternative splicing in the N-terminal region generates two isoforms, A13a and A13b, differing in a deletion of 41 residues in the former. We have confirmed the expression of both isoforms in human colon adenocarcinoma cells at the mRNA and protein levels...
September 27, 2016: Biological Chemistry
Jiayin Chen, Jürgen Brockmöller, Tina Seitz, Jörg König, Xijing Chen, Mladen V Tzvetkov
Tropane alkaloids and their derivatives are anticholinergic drugs with narrow therapeutic range. Here we characterize the organic cation transporters from the SLC22 (OCT1, OCT2, and OCT3) and the SLC47 families (MATE1 and MATE2-K) as potential mediators of the renal and extra-renal excretion, the two major roads of elimination of these substances. All analyzed compounds inhibited and the quaternary amine derivatives ipratropium and trospium were strongly transported by OCTs and MATEs. Overexpression of OCTs or MATEs in HEK293 cells resulted in up to 63-fold increase in the uptake of ipratropium (Km of 0...
September 27, 2016: Biological Chemistry
Susann Zilkenat, Iwan Grin, Samuel Wagner
Gaining knowledge of the structural makeup of protein complexes is critical to advance our understanding of their formation and functions. This task is particularly challenging for transmembrane protein complexes, and grows ever more imposing with increasing size of these large macromolecular structures. The last 10 years have seen a steep increase in solved high-resolution membrane protein structures due to both new and improved methods in the field, but still most structures of large transmembrane complexes remain elusive...
September 24, 2016: Biological Chemistry
Yutao Yang, Yueting Li, Fei Di, Jiajun Cui, Yue Wang, Zhi-Qing David Xu
Pokemon is a transcriptional repressor that belongs to the POZ and Krüppel (POK) protein family. In this study, we investigated the potential interaction between Pokemon and retinoic acid receptor alpha (RARα) and determined the role of Pokemon in regulation of RARα transcriptional activity in the absence of ligand. We found that Pokemon could directly interact with RARα. Moreover, we demonstrated that Pokemon could decrease the transcriptional activity of RARα in the absence of ligand. Furthermore, we showed that Pokemon could repress the transcriptional activity of RARα by increasing the recruitment of nuclear receptor co-repressor (NCoR) and silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) to the retinoic acid response element (RARE) element...
September 20, 2016: Biological Chemistry
Charlotte Toulouse, Björn Claussen, Valentin Muras, Günter Fritz, Julia Steuber
The Na+-translocating NADH:quinone oxidoreductase (NQR) is the entry site for electrons into the respiratory chain of Vibrio cholerae, the causative agent of cholera disease. NQR couples the electron transfer from NADH to ubiquinone to the translocation of sodium ions across the membrane. We investigated the pH dependence of electron transfer and generation of a transmembrane voltage (ΔΨ) by NQR reconstituted in liposomes with Na+ or Li+ as coupling cation. ΔΨ formation was followed with the voltage-sensitive dye oxonol...
September 17, 2016: Biological Chemistry
Patrick Ernst, Andreas Plückthun
The specific recognition of peptides, which we define to include unstructured regions or denatured forms of proteins, is an intrinsic part of a multitude of biochemical assays and procedures. Many cellular interactions are based on this principle as well. While it would be highly desirable to have a stockpile of sequence-specific binders for essentially any sequence, a de novo selection of individual binders against every possible target peptide sequence would be rather difficult to reduce to practice. Modular peptide binders could overcome this problem, as preselected and/or predesigned modules could be reused for the generation of new binders and thereby revolutionize the generation of binding proteins...
September 16, 2016: Biological Chemistry
Mareen Pagel, Annette G Beck-Sickinger
A controlled interaction of materials with their surrounding biological environment is of great interest in many fields. Multifunctional coatings aim the simultaneous modulation of several biological signals. They can consist of various combinations of bioactive, and bioinert components as well as of reporter molecules to improve cell-material contacts, prevent infections or to analyze biochemical events on the surface. However, specific immobilization and particular assembly of various active molecules are challenging...
September 16, 2016: Biological Chemistry
Christian Bolz, Nina C Bach, Hannelore Meyer, Gerhard Müller, Maciej Dawidowski, Grzegorz Popowicz, Stephan A Sieber, Arne Skerra, Markus Gerhard
Helicobacter pylori infects the stomach of 50% of the population worldwide, thus causing chronic gastritis. Although this infection can be cured by antibiotic treatment, therapeutic options are increasingly limited due to the development of resistances. The γ-glutamyltranspeptidase (gGT) of Helicobacter pylori (HpgGT) is a virulence factor important for colonization and contributes to bacterial immune evasion. Therefore, this enzyme is a potential target for developing new anti-infectives. As species specificity of such compounds is required in order to avoid off target or adverse effects, comparative analysis of the gGTs from different organisms is a prerequisite for drug development...
September 16, 2016: Biological Chemistry
Maximilian Neugebauer, Jana K Böcker, Julian C J Matern, Shmuel Pietrokovski, Henning D Mootz
Protein splicing by inteins has found diverse applications in biotechnology, protein chemistry and chemical biology. Inteins display a wide range of efficiencies and rates unpredictable from their amino acid sequences. Here, we identified positions T22S and S35 in the LacZα peptide as intein insertion sites that strictly require protein splicing, in contrast to cleavage side-reactions, to allow for complementation of β-galactosidase activity. Both the cis-variant of the M86 mutant of the Ssp DnaB intein and a split form undergoing protein trans-splicing gave rise to formation of blue colonies in the β-galactosidase read-out...
September 15, 2016: Biological Chemistry
Dorinne Desposito, Ludovic Waeckel, Louis Potier, Christine Richer, Ronan Roussel, Nadine Bouby, Francois Alhenc-Gelas
Genetic and pharmacological studies, clinical and experimental, focused on kallikrein-K1, kinin receptors and ACE/kininase II suggest that kinin release in the settings of ischemia or diabetes reduces organ damage, especially in the heart and kidney. Kinin bioavailability may be a limiting factor for efficacy of current kinin-potentiating drugs, like ACE inhibitors. Primary activation of kinin receptors by prototypic pharmacological agonists, peptidase-resistant, selective B1 or B2, displays therapeutic efficacy in experimental cardiac and peripheral ischemic and diabetic diseases...
September 13, 2016: Biological Chemistry
Ching-Wen Chang, Kanishk Abhinav, Francesca Di Cara, Ioanna Panagakou, Sharron Vass, Margarete M S Heck
Invadolysin is a novel metalloprotease conserved amongst metazoans that is essential for life in Drosophila. We previously showed that invadolysin was essential for the cell cycle and cell migration, linking to metabolism through a role in lipid storage and interaction with mitochondrial proteins. In this study we demonstrate that invadolysin mutants exhibit increased autophagy and decreased glycogen storage - suggestive of a role for invadolysin in insulin signaling in Drosophila. Consistent with this, effectors of insulin signaling were decreased in invadolysin mutants...
September 13, 2016: Biological Chemistry
Christine C Helms, Xiaohua Liu, Daniel B Kim-Shapiro
Nitrite was once thought to be inert in human physiology. However, research over the past few decades has established a link between nitrite and the production of nitric oxide (NO) that is potentiated under hypoxic and acidic conditions. Under this new role nitrite acts as a storage pool for bioavailable NO. The NO so produced is likely to play important roles in decreasing platelet activation, contributing to hypoxic vasodilation, and minimizing bloodcell adhesion to endothelial cells. Researchers have proposed multiple mechanisms for nitrite reduction in the blood...
September 9, 2016: Biological Chemistry
Janett Müller, Markus Keiser, Marek Drozdzik, Stefan Oswald
Although oral drug administration is nowadays the favourable route of administration, intestinal drug absorption is challenged by several highly variable and poorly predictable processes such as gastrointestinal motility, intestinal drug solubility and intestinal metabolism. One further determinant that have been identified and characterized during the last two decades is the intestinal drug transport that is mediated by several transmembrane proteins such as P-gp, BCRP, PEPT1 and OATP2B1. It is so far well-established that intestinal transporters can affect oral absorption of many drugs in a significant manner either by facilitating their cellular uptake or by pumping them back to gut lumen which limits their oral bioavailability...
September 9, 2016: Biological Chemistry
Mekdes Debela, Viktor Magdolen, Wolfram Bode, Hans Brandstetter, Peter Goettig
Although kallikrein-related peptidase 10 (KLK10) is expressed in a variety of human tissues and body fluids, knowledge of its physiological functions is fragmentary. Similarly, the pathophysiology of KLK10 in cancer is not well understood. In some cancer types, a role as tumor suppressor has been suggested, while in others elevated expression is associated with poor patient prognosis. Active human KLK10 exhibits a unique, three residue longer N-terminus with respect to other serine proteases and an extended 99-loop nearly as long as in tissue kallikrein KLK1...
September 9, 2016: Biological Chemistry
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