Acta Crystallogr Sect F Struct Biol Cryst Commun
February 2012
Dipeptidyl peptidase 10 (DPP10, DPPY) is an inactive peptidase associated with voltage-gated potassium channels, acting as a modulator of their electrophysiological properties, cell-surface expression and subcellular localization. Because potassium channels are important disease targets, biochemical and structural characterization of their interaction partners was sought. DPP10 was cloned and expressed using an insect-cell system and the protein was purified via His-tag affinity and size-exclusion chromatography.
View Article and Find Full Text PDFCarbohydrate-based sensors, that specifically detect sugar binding molecules or cells, are increasingly important in medical diagnostic and drug screening. Here we demonstrate that cantilever arrays functionalized with different mannosides allow the real-time detection of several Escherichia coli strains in solution. Cantilever deflection is thereby dependent on the bacterial strain studied and the glycan used as the sensing molecule.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
September 2011
Carbohydrates are important mediators of many biological processes that underlie cellular communication and disease mechanisms. Therapeutic agents include carbohydrate-based vaccines and the potent anti-viral protein Cyanovirin-N (CV-N). CV-N acts by specifically binding the carbohydrate structures decorating the cell surface of deadly viruses including human immunodeficiency virus (HI-V) or Ebola.
View Article and Find Full Text PDFA large strain collection comprising antagonistic bacteria was screened for novel detergent proteases. Several strains displayed protease activity on agar plates containing skim milk but were inactive in liquid media. Encapsulation of cells in alginate beads induced protease production.
View Article and Find Full Text PDFThe crystal structure and pro-inflammatory property of a lectin from the seeds of Dioclea wilsonii (DwL) were analyzed to gain a better understanding of structure/function relationships of Diocleinae lectins. Following crystallization and structural determination by standard molecular replacement techniques, DwL was found to be a tetramer based on PISA analysis, and composed by two metal-binding sites per monomer and loops which are involved in molecular oligomerization. DwL presents 96% and 99% identity with two other previously described lectins of Dioclea rostrata (DRL) and Dioclea grandiflora (DGL).
View Article and Find Full Text PDFObjectives: Neurofunctional alterations are correlates of vulnerability to psychosis, as well as of the disorder itself. How these abnormalities relate to different probabilities for later transition to psychosis is unclear. We investigated vulnerability- versus disease-related versus resilience biomarkers of psychosis during working memory (WM) processing in individuals with an at-risk mental state (ARMS).
View Article and Find Full Text PDFPurpose: The purpose of this study was to determine potential effects of isometric non-machine-based training on the cross-sectional area (CSA) of the paravertebral muscles in volunteers who were participants in a prevention program. An increase in the CSA of back muscles after various machine-based exercises have been reported but non-machine-based training programs have not been adressed before.
Materials And Methods: In the study 14 volunteers, who were participants of a company internal prevention program, underwent a magnetic resonance (MR) examination before and after a 3 months training program to improve back muscle strength.
As inhibitors of chitin synthase, nikkomycins have attracted interest as potential antibiotics. The biosynthetic pathway to these peptide nucleosides in Streptomyces tendae is only partially known. In order to elucidate the last step of the biosynthesis of the aminohexuronic building block, we have heterologously expressed a predicted aminotransferase encoded by the gene nikK from S.
View Article and Find Full Text PDFObjective: The HDL family forms a protective part of plasma lipoproteins. It consists of large HDL, intermediate HDL, and small HDL subclasses. The large HDL and intermediate HDL subclasses are considered anti-atherogenic parts of the HDL family.
View Article and Find Full Text PDFObjective: In the subjects, who survived a stroke, an atherogenic lipoprotein profile phenotype B, was identified and a predominance of atherogenic lipoproteins of the lipoprotein families, VLDL and LDL, in the lipoprotein spectrum, was confirmed. The higher total cholesterol, triglycerides, and low HDL concentrations were accompanied by high serum levels of small dense LDL - strong atherogenic subfractions of the LDL family. High LDL2 also contributes to the creation of the atherogenic lipoprotein profile.
View Article and Find Full Text PDFCobalamin (Cbl) is a complex cofactor produced only by bacteria but used by all animals and humans. Cyanocobalamin (vitamin B(12), CNCbl) is one commonly isolated form of cobalamin. B(12) belongs to a large group of corrinoids, which are characterized by a distinct red color conferred by the system of conjugated double bonds of the corrin ring retaining a Co(III) ion.
View Article and Find Full Text PDFIn metazoans, the highly conserved Notch pathway drives cellular specification. On receptor activation, the intracellular domain of Notch assembles a transcriptional activator complex that includes the DNA-binding protein CSL, a composite of human C-promoter binding factor 1, Suppressor of Hairless of Drosophila melanogaster [Su(H)], and lin-12 and Glp-1 phenotype of Caenorhabditis elegans. In the absence of ligand, CSL represses Notch target genes.
View Article and Find Full Text PDFObjective: The identification of an atherogenic and a non-atherogenic lipoprotein profile, athero phenotype B vs. non-athero phenotype A, in a group of healthy normolipidemic subjects reveals a new clinical phenomenon in lipoprotein profiles, an atherogenic normolipidemia. Individuals with atherogenic normolipidemia are at increased risk to develop premature atherothrombosis and experience a sudden cardiovascular event.
View Article and Find Full Text PDFObjective: The identification of a non-atherogenic and an atherogenic lipoprotein profile, non-athero phenotype A vs. athero phenotype B, in a group of hypercholesterolemic subjects reveals newly discovered non-atherogenic hypercholesterolemia. Individuals with this type of hypercholesterolemia, or hyper-betalipoproteinemia LDL1,2, are probably not at increased risk to develop a premature atherothrombosis or a sudden cardiovascular event.
View Article and Find Full Text PDFB(12)-cofactors play important roles in the metabolism of microorganisms, animals and humans. Microorganisms are the only natural sources of B(12)-derivatives, and the latter are "vitamins" for other B(12)-requiring organisms. Some B(12)-dependent enzymes catalyze complex isomerisation reactions, such as methylmalonyl-CoA mutase.
View Article and Find Full Text PDFAdvances in carbohydrate sequencing technologies have revealed the tremendous complexity of the glycome. This complexity reflects the structural and chemical diversity of carbohydrates and is greater than that of proteins and oligonucleotides. The next step in understanding the biological function of carbohydrates requires the identification and quantification of carbohydrate interactions with other biomolecules, in particular, with proteins.
View Article and Find Full Text PDFPrimary aldosteronism is common cause of secondary hypertension. As a result of high blood pressure it can lead to severe complications, including aortic dissection. We would like to present a case of 40 year-old patient who had resistant hypertension despite administration of multiple drugs.
View Article and Find Full Text PDFA large number of novel disease genes have been identified by homozygosity mapping and the positional candidate approach. In this study we used single nucleotide polymorphism (SNP) array-based, whole genome homozygosity mapping as the first step to a molecular diagnosis in the highly heterogeneous muscle disease, limb girdle muscular dystrophy (LGMD). In a consanguineous family, both affected siblings showed homozygous blocks on chromosome 15 corresponding to the LGMD2A locus.
View Article and Find Full Text PDFIn preparation for transfer conjugative type IV secretion systems (T4SS) produce a nucleoprotein adduct containing a relaxase enzyme covalently linked to the 5' end of single-stranded plasmid DNA. The bound relaxase is expected to present features necessary for selective recognition by the type IV coupling protein (T4CP), which controls substrate entry to the envelope spanning secretion machinery. We prove that the IncF plasmid R1 relaxase TraI is translocated to the recipient cells.
View Article and Find Full Text PDFAlthough glucocorticosteroids (GCSs) have been used for many decades in transplantation and (auto)inflammatory diseases, the exact mechanisms responsible for their immunosuppressive properties are not fully understood. The purpose of this study was to characterize the effects of oral GCSs on the cutaneous immune response. We analyzed, by immunofluorescence staining and quantitative RT-PCR, residual skin biopsy material from a clinical study in which we had used oral GCS as positive control for determining the effects of candidate anti-inflammatory compounds on epicutaneous patch tests of Ni-allergic patients.
View Article and Find Full Text PDFAn interaction-site model can a priori predict molecular self-organisation on a new substrate in Monte Carlo simulations. This is experimentally confirmed with scanning tunnelling microscopy on Fréchet dendrons of a pentacontane template. Local and global ordering motifs, inclusion molecules and a rotated unit cell are correctly predicted.
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