- Protein Structure and Dynamics
- Lipid Membrane Structure and Behavior
- HIV Research and Treatment
- Advanced NMR Techniques and Applications
- Receptor Mechanisms and Signaling
- HIV/AIDS drug development and treatment
- Glycosylation and Glycoproteins Research
- Neuroscience and Neuropharmacology Research
- Molecular spectroscopy and chirality
- Mosquito-borne diseases and control
- Photoreceptor and optogenetics research
- Cellular transport and secretion
- RNA and protein synthesis mechanisms
- Organometallic Complex Synthesis and Catalysis
- DNA and Nucleic Acid Chemistry
- Monoclonal and Polyclonal Antibodies Research
- Crystallography and molecular interactions
- Viral Infections and Vectors
- Coordination Chemistry and Organometallics
- Advanced biosensing and bioanalysis techniques
- Immune Cell Function and Interaction
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Viral Infections and Outbreaks Research
- Biotin and Related Studies
Forschungszentrum Jülich
2009-2020
Heinrich Heine University Düsseldorf
2008-2019
Inwood Community Services
2019
Stadtwerke Jülich (Germany)
2013
Cornell University
2007
National Institutes of Health
1996-2005
National Institute on Alcohol Abuse and Alcoholism
1997
Geophysical Laboratory
1995
University of Freiburg
1988
The interaction between receptors and guanine nucleotide binding (G) proteins leads to G protein activation subsequent regulation of effector enzymes. molecular basis receptor-G has been examined by using the ability from rods (transducin) cause a conformational change in rhodopsin as an assay. Synthetic peptides corresponding two regions near carboxyl terminus α subunit, Glu 311 -Val 328 Ile 340 -Phe 350 , compete with for rhodopsin. Amino acid substitution studies show that Cys 321 is...
Specular reflection of neutrons has been used to characterize the structure single lipid bilayers adsorbed a planar silicon surface from aqueous solution. We novel experimental setup which significantly decreased incoherent background scattering and allowed us measure neutron reflectivities as low 5 × 10-7. Thicknesses length densities were determined by fitting procedure using (i) randomly generated smooth functions represented parametric B-splines (ii) stepped based on theoretical...
The immunophilin-like FKBP42 TWISTED DWARF1 (TWD1) has been shown to control plant development via the positive modulation of ABCB/P-glycoprotein (PGP)-mediated transport hormone auxin. TWD1 functionally interacts with two closely related proteins, ABCB1/PGP1 and ABCB19/PGP19/MDR1, both which exhibit ability bind be inhibited by synthetic auxin inhibitor N-1-naphylphtalamic acid (NPA). They are also flavonoid compounds, suspected modulators transport. mechanisms flavonoids NPA interfere...
We present a two-dimensional solution NMR spectrum of an integral membrane protein (IMP) in nanodisc. Solution relies on rapid isotropic tumbling the analyte with correlation times nanosecond range. IMPs cellular do not satisfy this condition. Previous liquid-state studies were conducted organic solvent or artificial mimicking particles like detergent micelles. Nanodiscs are relatively small (150 kDa), detergent-free model membranes that suitable for functional reconstitution IMPs. allow...
Background: The fast development of microbial production strains for basic and fine chemicals is increasingly carried out in small scale cultivation systems to allow higher throughput. Such parallelized create a need new rapid online detection quantify the respective target compound. In this regard, biosensors, especially genetically encoded Förster resonance energy transfer (FRET)-based offer tremendous opportunities. As proof-of-concept, we have created toolbox FRET-based biosensors...
Thiazolo-iso-indolinone derivatives with high specificity toward the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) were identified. The most potent compound, BM +51.0836, inhibited HIV-1 RT at a 50% inhibitory concentration 90 nM in vitro. In cell culture assays, similar concentrations obtained for HIV-1. These substances equally active against zidovudine-resistant isolate. No antiviral effect was observed an HIV-2 isolates resistant to thiazolo-iso-indolinones...
Binding of arrestin to photoactivated phosphorylated rhodopsin terminates the amplification visual signals in photoreceptor cells. Currently, there is no crystal structure a rhodopsin−arrestin complex available, although structures unbound and have been determined. High-affinity receptor binding dependent on distinct sites responsible for recognition activation phosphorylation. The loop connecting β-strands V VI rod has implicated active rhodopsin. We report receptor-bound peptide Arr(67−77)...
Molecular dynamics plays an important role for the biological function of proteins. For protein ligand interactions, changes conformational entropy and hydration layer are relevant binding process. Quasielastic neutron scattering (QENS) was used to investigate differences in ligand-bound ligand-free streptavidin. Protein were probed both on fast picosecond time scale using time-of-flight spectroscopy slower nanosecond high-resolution backscattering spectroscopy. We found internal equilibrium...
N-myristoylation is a crucial covalent modification of numerous eukaryotic and viral proteins that catalyzed by N-myristoyltransferase (NMT). Prokaryotes are lacking endogenous NMT activity. Recombinant production N-myristoylated in E. coli cells can be achieved coexpression heterologous with the target protein. In past, dual plasmid systems were used for this purpose.Here we describe single vector system efficient substrate enzyme suitable co- or posttranslationally modified proteins. The...
Dengue virus (DENV) is an important human pathogen causing millions of disease cases and thousands deaths worldwide. Non-structural protein 4A (NS4A) a vital component the viral replication complex (RC) plays major role in formation host cell membrane-derived structures that provide scaffold for replication. The N-terminal cytoplasmic region NS4A(1-48) known to preferentially interact with highly curved membranes. Here, we experimental evidence stable binding small liposomes using liposome...
Thermophoretic behavior of a free protein changes upon ligand binding and gives access to information on the constants. The Soret effect has also been proven be promising tool gain hydration layer, as temperature dependence thermodiffusion is sensitive solute-solvent interactions. In this work, we perform systematic thermophoretic measurements streptavidin (STV) complex STV with biotin (B) using thermal diffusion forced Rayleigh scattering (TDFRS). Our experiments show that sensitivity...
Since its discovery as a crucial cocatalyst in metallocene and post-metallocene olefin polymerizations methylaluminoxane (MAO) has retained commercial academic status. In spite of continued interest the MAO structure remains ambiguously defined. Because limited alkane solubility toluene emerged solvent necessity. With time these solutions can develop gel fraction. The structures proposed include linear, ring, ladder, cyclic with latter involving fused four six membered rings along cage...
The HIV-1 encoded virus protein U (VpU) is required for efficient viral release from human host cells and induction of CD4 degradation in the endoplasmic reticulum. cytoplasmic domain membrane VpU (VpUcyt) essential latter activity. structure dynamics VpUcyt were characterized presence simulating dodecylphosphatidylcholine (DPC) micelles by high-resolution liquid state NMR. unstructured aqueous buffer. addition DPC induces a well-defined proximal alpha-helix (residues I39-E48) an additional...
The role of tryptophan as a key residue for ligand binding to the ubiquitin-like modifier GABA(A) receptor associated protein (GABARAP) was investigated. Two tryptophan-binding hydrophobic patches were identified on conserved face GABARAP structure by NMR spectroscopy and molecular docking. indole derivatives, including free amino acid quantified. two sites can be clearly distinguished mapping spectroscopy-derived residue-specific apparent dissociation constant, K(d), onto three-dimensional...
Viral protein U ( V p ) of HIV ‐1 plays an important role in downregulation the main receptor CD 4 from surface infected cells. Physical binding to newly synthesized endoplasmic reticulum is early step a pathway leading proteasomal degradation 4. In this study, regions cytoplasmic domain involved were identified by NMR spectroscopy. Amino acids both helices found region membrane‐mimicking detergent micelles experience chemical shift perturbations upon 4, whereas amino between two and at C...
Sterile alpha motif (SAM) domains are protein interaction modules that involved in a diverse range of biological functions such as transcriptional and translational regulation, cellular signalling, regulation developmental processes. SH3 domain-containing expressed lymphocytes 1 (SLy1) is immune contains SAM domain unknown function. In this report, the structure SLy1 was solved revealed forms symmetric homodimer through novel interface. The interface consists primarily two long C-terminal...
The interaction of ethanol with phospholipids was studied in bicelles at a physiologically relevant concentration 20 mM and lipid content 14 wt % by high-resolution NMR. Transient association magnetically aligned imparts small degree anisotropy to the solute. This allows detection residual (1)H-(1)H (1)H-(13)C dipolar couplings, which are superimposed on scalar couplings. Residual (2)H NMR quadrupole splittings isotope-labeled were measured as well. analysis tensorial interactions yielded...