A5065411141- Enzyme Structure and Function
- Biochemical and Molecular Research
- Advanced Electron Microscopy Techniques and Applications
- Microbial Natural Products and Biosynthesis
- Protein Structure and Dynamics
- Bioactive Compounds and Antitumor Agents
- Electrochemical sensors and biosensors
- Electron and X-Ray Spectroscopy Techniques
- Computational Drug Discovery Methods
- Synthesis of heterocyclic compounds
- Pharmacogenetics and Drug Metabolism
- Mass Spectrometry Techniques and Applications
- Synthesis and biological activity
- ATP Synthase and ATPases Research
- Microbial Metabolism and Applications
- Microbial Fuel Cells and Bioremediation
- Plant biochemistry and biosynthesis
- X-ray Diffraction in Crystallography
- Photosynthetic Processes and Mechanisms
Swiss Light Source
2024
Paul Scherrer Institute
2023-2024
University of Hohenheim
2020-2023
University of Tübingen
2017
Over the last two decades, fragment-based drug discovery (FBDD) has emerged as an effective and efficient method to identify new chemical scaffolds for development of lead compounds. X-ray crystallography can be used in FBDD a tool validate develop fragments identified binders by other methods. However, it is also often with great success primary screening technique. In recent years, technological advances at macromolecular beamlines terms instrumentation, beam intensity robotics have...
Abstract Metalloproteinase inhibitors often feature hydroxamate moieties to facilitate the chelation of metal ions in catalytic center target enzymes. Actinonin and matlystatins are potent metalloproteinase that comprise rare N -hydroxy-2-pentyl-succinamic acid warheads. Here we report identification characterization their biosynthetic pathways. By gene cluster comparison a combination precursor feeding studies, heterologous pathway expression deletion experiments able show...
The Swiss Light Source facilitates fragment-based drug-discovery campaigns for academic and industrial users through the Fast Fragment Compound Screening (FFCS) software suite. This framework is further enriched by option to utilize Smart Digital User (SDU) automated data collection across PXI, PXII PXIII beamlines. In this work, newly developed HEIDI webpage (https://heidi.psi.ch) introduced: a platform crafted using state-of-the-art architecture web technologies sample management of...
Ruminants such as cattle and sheep depend on the breakdown of carbohydrates from plant-based feedstuff, which is accomplished by microbial community in rumen. Roughly 40% members rumen microbiota belong to family Prevotellaceae, ferments sugars organic acids acetate, propionate, succinate. These substrates are important nutrients for ruminant. In a metaproteome analysis cattle, proteins that homologous Na+-translocating NADH:quinone oxidoreductase (NQR) quinone:fumarate reductase (QFR) were...
X-ray free-electron laser (XFEL) light sources have enabled the rapid growth of time-resolved structural experiments, which provide crucial information on function macromolecules and their mechanisms. Here, aim was to commission SwissMX fixed-target sample-delivery system at SwissFEL Cristallina experimental station using PSI-developed micro-structured polymer (MISP) chip for pump-probe experiments. To characterize system, crystals light-sensitive protein light-oxygen-voltage domain 1 (LOV1)...
Abstract X-ray free electron laser (XFEL) light sources have allowed for the rapid growth of time-resolved structural experiments, which provide crucial information on function biological machines and their mechanisms. We set out to commission SwissMX fixed-target sample delivery system at SwissFEL Cristallina experimental station using PSI developed MISP-chip pump-probe experiments. To characterise system, we used light-sensitive protein crystals Light-Oxygen-Voltage domain 1 (LOV1) from...
A short, efficient one-step synthesis of 2-methyl-5-(3-methyl-2-butenyl)-1,4-benzoquinone, a natural product from Pyrola media is described. The based on direct late C-H functionalization the quinone scaffold. formation was confirmed by means 2D-NMR spectroscopy. Additional derivatives were synthesized and tested alongside as potential substrate substrate-based inhibitors mitochondrial complex I (MCI). structure-activity relationship study led to discovery...
Over the last two decades, fragment-based drug discovery has emerged as an effective and efficient method to identify chemical scaffolds for development of novel lead compounds.The inherent "start small -elaborate efficiently" approach allows issues like compound-selectivity, toxicity efficiency be addressed from a very early state on, while saving time resources compared classical high throughput screening larger compounds.X-ray crystallography been used long important orthogonal validating...