Search results for "binding"
showing 10 items of 3896 documents
Post-translational modifications in the survival motor neuron protein
2004
Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by a progressive loss of the spinal motoneurons. The SMA-determining gene has been termed survival motor neuron (SMN) and is deleted or mutated in over 98% of patients. The encoded gene product is a protein expressed as different isoforms. In particular, we showed that the rat SMN cDNA produces two isoforms with Mr of 32 and 35 kDa, both localized in nuclear coiled bodies, but the 32 kDa form is also cytoplasmic, whereas the 35 kDa form is also microsomal. To determine the molecular relationship between these two isoforms and potential post-translational modifications, we performed transfection experiments with a …
Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption
2015
Contains fulltext : 155360.pdf (Publisher’s version ) (Closed access) Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91,462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and b…
High-precision Penning-trap mass measurements of heavy xenon isotopes for nuclear structure studies
2009
With the double Penning-trap mass spectrometer ISOLTRAP at ISOLDE/CERN the masses of the neutron-rich isotopes $^{136\ensuremath{-}146}\mathrm{Xe}$ were measured with a relative uncertainty of the order of ${10}^{\ensuremath{-}8}$ to ${10}^{\ensuremath{-}7}$. In particular, the masses of $^{144\ensuremath{-}146}\mathrm{Xe}$ were measured for the first time. These new mass values allow one to extend calculations of the mass surface in this region. Proton-Neutron interaction strength, obtained from double differences of binding energies, relate to subtle structural effects, such as the onset of octupole correlations, the growth of collectivity, and its relation to the underlying shell model l…
Structure and function of the vacuolar Ccc1/VIT1 family of iron transporters and its regulation in fungi
2020
Iron is an essential micronutrient for most living beings since it participates as a redox active cofactor in many biological processes including cellular respiration, lipid biosynthesis, DNA replication and repair, and ribosome biogenesis and recycling. However, when present in excess, iron can participate in Fenton reactions and generate reactive oxygen species that damage cells at the level of proteins, lipids and nucleic acids. Organisms have developed different molecular strategies to protect themselves against the harmful effects of high concentrations of iron. In the case of fungi and plants, detoxification mainly occurs by importing cytosolic iron into the vacuole through the Ccc1/V…
Anti-Idiotypic Antibodies Against the Kinin Receptor
1992
Three sets of monoclonal antibodies against bradykinin (MBK1, MBK2, MBK3) were generated by somatic cell fusion, characterized by their peptide specificity and compared to the known ligand specificity of the kinin receptor subtypes. By these criteria the paratope of MBK3 resembled the B2 receptor binding site whereas MBK1 shared principal binding characteristics with the B1 recrptor. Anti-idiotypic antibodies against MBK1, MBK2 and MBK3 were raised in rabbit and sheep. Specificity of the network components was verified by inhibition experiments on the level of peptide, idiotype and anti-idiotype. Anti-idiotypic antibodies against MBK3 recognized a conformation-dependent epitope which was bi…
Structural Determinants for the Mode of Action of Imidazopyridine DS2 at δ-Containing γ-Aminobutyric Acid Type A Receptors
2021
Despite the therapeutic relevance of δ-containing γ-aminobutyric acid type A receptors (GABAARs) and the need for δ-selective compounds, the structural determinants for the mode and molecular site of action of δ-selective positive allosteric modulator imidazo[1,2-a]pyridine DS2 remain elusive. To guide the quest for insight, we synthesized a series of DS2 analogues guided by a structural receptor model. Using a fluorescence-based fluorometric imaging plate reader membrane potential assay, we found that the δ-selectivity and the pharmacological profile are severely affected by substituents in the 5-position of the imidazopyridine core scaffold. Interestingly, the 5-methyl, 5-bromo, and 5-chl…
Inhibition of the Cysteine Protease Human Cathepsin L by Triazine Nitriles: Amide⋅⋅⋅Heteroarene π-Stacking Interactions and Chalcogen Bonding in the …
2016
We report an extensive "heteroarene scan" of triazine nitrile ligands of the cysteine protease human cathepsin L (hCatL) to investigate π-stacking on the peptide amide bond Gly67-Gly68 at the entrance of the S3 pocket. This heteroarene⋅⋅⋅peptide bond stacking was supported by a co-crystal structure of an imidazopyridine ligand with hCatL. Inhibitory constants (Ki ) are strongly influenced by the diverse nature of the heterocycles and specific interactions with the local environment of the S3 pocket. Binding affinities vary by three orders of magnitude. All heteroaromatic ligands feature enhanced binding by comparison with hydrocarbon analogues. Predicted energetic contributions from the ori…
Comparative study on the inhibition of Na+, K+-activated ATPase activity by chlorpromazine, promazine, imipramine, and their monodesmethyl metabolites
1972
The inhibition of the sodium- and potassium-activated adenosine triphosphatase (Na-K-ATPase, EC 3.6.1.3) activity by chlorpromazine, promazine and imipramine was compared with that by the monodesmethyl metabolites of these drugs. The experiments were performed with a deoxycholate- and sodium iodide-treated microsomal enzyme preparation from rat brain. It was shown in dose-response curves as well as in double-reciprocal Lineweaver-Burk plots of Na-K-ATPase activity against KCl concentration that the monodesmethyl metabolites were stronger inhibitors than their parent compounds. The results obtained with the desmethyl metabolites and imipramine as inhibitors indicate competitive inhibition wh…
Neurotrophic Properties of Silexan, an Essential Oil from the Flowers of Lavender-Preclinical Evidence for Antidepressant-Like Properties.
2020
Abstract Background Silexan, a special essential oil from flowering tops of lavandula angustifolia, is used to treat subsyndromal anxiety disorders. In a recent clinical trial, Silexan also showed antidepressant effects in patients suffering from mixed anxiety-depression (ICD-10 F41.2). Since preclinical data explaining antidepressant properties of Silexan are missing, we decided to investigate if Silexan also shows antidepressant-like effects in vitro as well as in vivo models. Methods We used the forced swimming test (FST) in rats as a simple behavioral test indicative of antidepressant activity in vivo. As environmental events and other risk factors contribute to depression through conve…
Improved antifouling properties and selective biofunctionalization of stainless steel by employing heterobifunctional silane-polyethylene glycol over…
2016
AbstractA straightforward solution-based method to modify the biofunctionality of stainless steel (SS) using heterobifunctional silane-polyethylene glycol (silane-PEG) overlayers is reported. Reduced nonspecific biofouling of both proteins and bacteria onto SS and further selective biofunctionalization of the modified surface were achieved. According to photoelectron spectroscopy analyses, the silane-PEGs formed less than 10 Å thick overlayers with close to 90% surface coverage and reproducible chemical compositions. Consequently, the surfaces also became more hydrophilic, and the observed non-specific biofouling of proteins was reduced by approximately 70%. In addition, the attachment of E…