A5032832334- Protein Structure and Dynamics
- Neurobiology and Insect Physiology Research
- Chemical Reactions and Isotopes
- DNA and Nucleic Acid Chemistry
- Ion channel regulation and function
- Lipid Membrane Structure and Behavior
- Marine Toxins and Detection Methods
- Enzyme Catalysis and Immobilization
- RNA and protein synthesis mechanisms
- Microbial bioremediation and biosurfactants
- Genetics, Aging, and Longevity in Model Organisms
- Spectroscopy and Quantum Chemical Studies
- Phosphorus and nutrient management
- Nicotinic Acetylcholine Receptors Study
- Microbial metabolism and enzyme function
- Distributed and Parallel Computing Systems
- Hemoglobin structure and function
- Epigenetics and DNA Methylation
- Enzyme Structure and Function
- Biochemical Analysis and Sensing Techniques
- Protein Interaction Studies and Fluorescence Analysis
- Biofield Effects and Biophysics
- Surfactants and Colloidal Systems
- Atmospheric chemistry and aerosols
- CRISPR and Genetic Engineering
University of Michigan
2015-2020
Michigan United
2017-2019
Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry
2011-2019
Ann Arbor Center for Independent Living
2019
Czech Academy of Sciences
2012-2014
University of South Bohemia in České Budějovice
2011-2013
Czech Academy of Sciences, Global Change Research Institute
2013
Recent studies find that sugar tastes less intense to humans with obesity, but whether this sensory change is a cause or consequence of obesity unclear. To tackle question, we study the effects high diet on sweet taste sensation and feeding behavior in Drosophila melanogaster. On diet, fruit flies have lower responses stimuli, overconsume food, develop obesity. Excess dietary sugar, not sweetness alone, caused deficits overeating via cell-autonomous action sensor O-linked N-Acetylglucosamine...
Mutations targeting as few four residues lining the access tunnel extended half-life of an enzyme in 40 % dimethyl sulfoxide from minutes to weeks and increased its melting temperature by 19 °C. Protein crystallography molecular dynamics revealed that residue packing is a key determinant protein stability active-site accessibility for cosolvent molecules (red dots).
Abstract Metabolites are active controllers of cellular physiology, but their role in complex behaviors is less clear. Here we report metabolic changes that occur during the transition between hunger and satiety Drosophila melanogaster . To analyze these data context fruit fly networks, developed Flyscape, an open-access tool. We show response to eating, profiles change quick, distinct ways heads bodies. Consumption a high sugar diet dulls behavioral differences fasted fed state, reshapes...
Diets high in sugar persistently alter sensory responses to sweetness through the actions of PRC2 complex promote obesity.
A time-dependent fluorescence shift method, biomimetic colorimetric assays, and molecular dynamics simulations have been performed in search of explanations why arginine rich peptides with intermediate lengths about 10 amino acids translocate well through cellular membranes, while analogous lysine do not. First, we demonstrate that an important factor for efficient peptide adsorption, as the first prerequisite translocation across membrane, is presence negatively charged phospholipids...
Abstract The use of enzymes for biocatalysis can be significantly enhanced by using organic cosolvents in the reaction mixtures. Selection cosolvent type and concentration range an enzymatic is challenging requires extensive empirical testing. An understanding protein–solvent interaction could provide a theoretical framework rationalising selection process. Here, behaviour three model (haloalkane dehalogenases) was investigated presence representative (acetone, formamide, isopropanol)....
Transcriptional regulation allows cells to match their gene expression profiles current requirements based on environment, cellular physiological state, and extracellular signals. DNA binding transcription factors are major agents of transcriptional regulation, bind with a factor-specific sequence preference exert regulatory effects. A crucial step in unraveling the logic network is determining sequence-specific affinity landscapes for it. While such can be measured experimentally, ability...
Charybdotoxin, belonging to the group of so-called scorpion toxins, is a short peptide able block many voltage-gated potassium channels, such as mKv1.3, with high affinity. We use reliable homology model based on high-resolution crystal structure 94% sequence identical homologue Kv1.2 for charybdotoxin docking followed by molecular dynamics simulations investigate mechanism and energetics unbinding, tracing behavior channel protein during umbrella-sampling moved away from binding site. The...
The efficient oxidation of iodide and bromide at the aqueous solution-air interface ocean or sea spray aerosol particles had been suggested to be related their surface propensity. ubiquitous presence organic material calls for an assessment impact often surface-active compounds on interfacial density halide ions. We used in situ X-ray photoelectron spectroscopy with a liquid micro-jet obtain chemical composition information solution-vapor interfaces from mixed solutions containing 1-butanol...
The effect of the pore-blocking peptides charybdotoxin and margatoxin, both scorpion toxins, on currents through human voltage-gated hKv1.3 wild-type hKv1.3_H399N mutant potassium channels was characterized by whole-cell patch clamp technique. In channels, toxins hardly blocked current although they did prevent C-type inactivation slowing down decay during depolarization. Molecular dynamics simulations suggested that fast in channel a consequence amino acid reorientations behind selectivity...
Mutationen von vier Resten entlang des Zugangstunnels verlängerten die Halbwertzeit eines Enzyms in 40 % Dimethylsulfoxid Minuten zu Wochen und erhöhten Schmelztemperatur um 19 °C. Proteinkristallographie Moleküldynamik zeigen, dass Packung der Tunnelreste entscheidend für Proteinstabilität Zugänglichkeit aktiven Zentrums Cosolvens-Moleküle (rote Punkte) ist. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer...
Sequence-specific DNA binding transcription factors play an essential role in the transcriptional regulation of all organisms. The development reliable silico methods to predict affinity landscapes thus promises provide rapid screening factor specificities and, at same time, yield valuable insight into atomistic details interactions driving those specificities. Recent literature has reported highly discrepant results on current ability state-of-the-art molecular dynamics simulations...
Abstract Diets rich in sugar, salt, and fat alter taste perception food intake, leading to obesity metabolic disorders, but the molecular mechanisms through which this occurs are unknown. Here we show that response a high sugar diet, epigenetic regulator Polycomb Repressive Complex 2.1 (PRC2.1) persistently reprograms sensory neurons of D. melanogaster flies reduce sweet sensation promote obesity. In animals fed binding PRC2.1 chromatin gustatory is redistributed repress developmental...
Abstract The Polycomb-group proteins (PcG) and Trithorax-group (TrxG) are two major epigenetic regulators important for proper differentiation during development (1, 2). In Drosophila melanogaster ( D. ), Polycomb response elements (PREs) short segments of DNA with a high density binding sites transcription factors (TFs) that recruit PcG TrxG to chromatin. Each PRE has different number TrxG, these have topological organizations. It is thus difficult find general rules discover the locations...
Type1 restriction modification system are intriguing multifunctional multisubunit molecular motors that can catalyze both and activity. The type 1 RM enzymes binds to its target sequence activity as an endonuclease or methyltransferase is determined by the methylation state of sequence. If unmodified, enzyme while bound site believed translocate pull DNA towards itself simultaneously in directions ATP dependent manner. The crystal structure motor subunit R has been our group but mechanism...