A5028974311- Electron Spin Resonance Studies
- Lipid Membrane Structure and Behavior
- Lanthanide and Transition Metal Complexes
- Advanced NMR Techniques and Applications
- Protein Structure and Dynamics
- Cell Adhesion Molecules Research
- Supramolecular Chemistry and Complexes
- Coronary Interventions and Diagnostics
- Immune Response and Inflammation
- Consumer Retail Behavior Studies
- Spectroscopy and Quantum Chemical Studies
- Chemical Synthesis and Analysis
- Bacterial Genetics and Biotechnology
- Antibiotic Resistance in Bacteria
- RNA and protein synthesis mechanisms
- Electrochemical Analysis and Applications
- DNA and Nucleic Acid Chemistry
- Inorganic and Organometallic Chemistry
- Antimicrobial Resistance in Staphylococcus
- S100 Proteins and Annexins
- Antibiotics Pharmacokinetics and Efficacy
- Mitochondrial Function and Pathology
- Cytokine Signaling Pathways and Interactions
- Analytical Chemistry and Chromatography
- Immune Cell Function and Interaction
National Institutes of Health
2015-2025
Universitätsmedizin Greifswald
2019-2025
National Institute of Diabetes and Digestive and Kidney Diseases
2015-2025
University of Southern California
2011-2024
German Center for Neurodegenerative Diseases
2020-2021
Center for Biologics Evaluation and Research
2020
United States Food and Drug Administration
2020
Life & Brain (Germany)
2016-2018
University of Bonn
1995-2016
Philipps University of Marburg
2015-2016
ADVERTISEMENT RETURN TO ISSUEPREVArticleCatenanes and Rotaxanes of the Amide TypeFritz Vögtle, Thomas Dünnwald, SchmidtView Author Information Institut für Organische Chemie und Biochemie der Universität Bonn, Gerhard-Domagk-Strasse 1, 53121 Germany Cite this: Acc. Chem. Res. 1996, 29, 9, 451–460Publication Date (Web):September 11, 1996Publication History Received19 January 1996Published online11 September inissue 11...
Abstract Current distance measurements between spin‐labels on multimeric protonated proteins using double electron–electron resonance (DEER) EPR spectroscopy are generally limited to the 15–60 Å range. Here we show how DEER experiments can be extended dipolar evolution times of ca. 80 μs, permitting distances up 170 accessed in proteins. The method relies sparse spin‐labeling, supplemented by deuteration protein and solvent, minimize deleterious impact multispin effects substantially...
At the beginning of each molecular dynamics membrane simulation stands generation a suitable starting structure which includes working steps aligning and protein seamlessly accommodating in membrane. Here we introduce two efficient complementary methods based on pre-equilibrated patches, automating these steps. Using voxel-based cast coarse-grained protein, LAMBADA computes hydrophilicity profile-derived scoring function optimal rotation translation operations are determined to align...
To estimate the seroprevalence and temporal course of SARS-CoV-2 neutralizing antibodies, we embedded a multi-tiered survey within an ongoing community-based cohort study in Bonn, Germany. We first assessed anti-SARS-CoV-2 immunoglobulin G levels with immunoassay, followed by confirmatory testing borderline positive test results recombinant spike-based immunofluorescence assay plaque reduction neutralization (PRNT). Those or immunoassay result were retested after 4 to 5 months. At baseline,...
The N-terminal region of the huntingtin protein, encoded by exon-1, comprises an amphiphilic domain (htt NT ), a polyglutamine (Q n ) tract, and proline-rich sequence. Polyglutamine expansion results in aggregation-prone protein responsible for Huntington’s disease. Here, we study earliest events involved oligomerization minimalistic construct, htt Q 7 , which remains largely monomeric over sufficiently long period time to permit detailed quantitative NMR analysis kinetics structure sparsely...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTEnantiomeric Resolution of Cycloenantiomeric Rotaxane, Topologically Chiral Catenane, and Pretzel-Shaped Molecules: Observation Pronounced Circular DichroismChiyo Yamamoto, Yoshio Okamoto, Thomas Schmidt, Ralf Jäger, Fritz VögtleView Author Information Department Applied Chemistry Faculty Engineering, Nagoya University Furo-Cho, Chikusa-Ku, 464-01, Japan Kekulé-Institut für Organische Chemie und Biochemie der Universität Bonn...
SET and MYND domain containing protein 3 (SMYD3) is a histone methyltransferase, which has been implicated in cell growth cancer pathogenesis. Increasing evidence suggests that SMYD3 can influence distinct oncogenic processes by acting as gene-specific transcriptional regulator. However, the mechanistic aspects of transactivation whether acts concert with other transcription modulators remain unclear. Here, we show interacts human positive coactivator 4 (PC4) such interaction potentiates...
The family of genes implicated in hereditary spastic paraplegias (HSPs) is quickly expanding, mostly owing to the widespread availability next-generation DNA sequencing methods. Nevertheless, a genetic diagnosis remains unavailable for many patients.
Both intracellular and extracellular heat shock protein-90 (Hsp90) family proteins (α β) have been shown to support tumour progression. The tumour-supporting activity of the Hsp90 is attributed their N-terminal ATPase-driven chaperone function. What molecular entity determines function secreted distinction between Hsp90α Hsp90β was unclear. Here we demonstrate that CRISPR/Case9 knocking out nullifies cells’ ability migrate, invade metastasize without affecting cell survival growth. Knocking...
Significance Complex formation between calmodulin and target proteins underlies numerous calcium signaling processes in biology, yet structural mechanistic details, which entail major conformational changes both its substrates, have been unclear. We show that a combination of time-resolved electron paramagnetic NMR measurements can elucidate the molecular mechanism, at quantitative kinetic levels, binding pathway peptide substrate from skeletal muscle myosin light-chain kinase to...
Antibody‐based pharmaceuticals are the leading biologic drug platform (> $75B/year). Despite a wealth of information collected on them, there is still lack knowledge their inter‐domain structural distributions, which impedes innovation and development. To address this measurement gap, we have developed new methodology to derive biomolecular structure ensembles from distance distribution measurements via library tagged proteins bound an unlabeled otherwise unmodified target biologic. We...
Biodegradable polymers produced by renewable sources as polylactide-ε-caprolactone equipped with antimicrobial poly(hexamethylene biguanide) are suitable materials for medical devices.
Abstract Objectives High-risk human papillomavirus (HPV) infection leads to the development of several cancers that cause significant morbidity and mortality worldwide. HPV type 16 (HPV16) is most common cancer-causing genotypes gains entry basal cells epithelium through a non-canonical endocytic pathway involves annexin A2/S100A10 heterotetramer (A2t). A2t composed two A2 monomers bound an S100A10 dimer this interaction potential target block HPV16 infection. Here, recently identified small...
Expansion of the polyglutamine (polyQ) tract in exon 1 huntingtin protein (Httex1) leads to Huntington's disease resulting fatal neurodegeneration. However, it remains poorly understood how polyQ expansions alter structure and cause toxicity. Using CD, EPR, NMR spectroscopy, we found here that monomeric Httex1 consists two co-existing structural states whose ratio is determined by length. We observed short Q-lengths favor a largely random-coil state, whereas long increase proportion...
Lipid-based micellar nanoparticles promote aggregation of huntingtin exon-1 peptides. Here we characterize the interaction two such peptides, httNTQ 7 and 10 comprising N-terminal amphiphilic domain followed by glutamine repeats, respectively, with 8 nm lipid micelles using NMR chemical exchange saturation transfer (CEST), circular dichroism pulsed Q-band EPR. Exchange between free micelle-bound n peptides occurs on millisecond time scale a KD ∼ 0.5–1 mM. Upon binding micelles, residues 1–15...
G protein-coupled receptors (GPCR) activate numerous intracellular signaling pathways. The oligomerization properties of GPCRs, and hence their cellular functions, may be modulated by various components within the cell membrane (such as presence cholesterol). Modulation occur directly via specific interaction with GPCR or indirectly affecting physical membrane. Here, we use pulsed Q-band double electron–electron resonance (DEER) spectroscopy to probe distances between R1 nitroxide spin...
Abstract The first rotaxanes 6a, 6b and 11 with an amide structure are described. Their (supramolecular template) syntheses strikingly simple. central part of the „axle”︁ is added to „wheel”︁ subsequently capped. macromonocycle („wheel”︁) provides receptor cavity for triphenylmethane stoppers confirm mechanical bond between „axle”︁.
Abstract In membrane proteins, proline-mediated helix kinks are indispensable for the tight packing of transmembrane (TM) helices. However, invariably affect numerous interhelical interactions, questioning acceptance proline substitutions and evolutionary origin kinks. Here, we present structural thermodynamic basis proline-induced integrin αIIbβ3 TM complex stabilization to understand introduction in proteins. phospholipid bicelles, A711P substitution center β3 changes direction adjacent...
Abstract Salts and proteins comprise two of the basic molecular components biological materials. Kosmotropic/chaotropic co-solvation matching ion water affinities explain ionic effects on protein aggregation observed in simple solutions. However, it is unclear how these theories apply to complex environments what underlying binding patterns are. Using positive Ca 2+ negatively charged membrane SNAP25, we studied oligomerization solution, native membranes dynamics (MD) simulations. We find...