A5006674273- Peptidase Inhibition and Analysis
- Biochemical and Structural Characterization
- Connective tissue disorders research
- Bacterial Genetics and Biotechnology
- Protein Tyrosine Phosphatases
- Antibiotic Resistance in Bacteria
- Antimicrobial Resistance in Staphylococcus
- Ubiquitin and proteasome pathways
- Bacteriophages and microbial interactions
- Adenosine and Purinergic Signaling
- Protease and Inhibitor Mechanisms
- bioluminescence and chemiluminescence research
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Enzyme Production and Characterization
- Supramolecular Self-Assembly in Materials
- NF-κB Signaling Pathways
- Chemical Reactions and Isotopes
- Cytokine Signaling Pathways and Interactions
- ATP Synthase and ATPases Research
- Chemokine receptors and signaling
- Cell death mechanisms and regulation
- Click Chemistry and Applications
- Computational Drug Discovery Methods
- Bacterial biofilms and quorum sensing
Max Planck Computing and Data Facility
2018-2021
Technical University of Munich
2015-2021
Center for Integrated Protein Science Munich
2015-2021
Caseinolytic protease P (ClpP) represents a central bacterial degradation machinery that is involved in cell homeostasis and pathogenicity. The functional role of ClpP has been studied by genetic knockouts through the use beta-lactones, which remain only specific inhibitors discovered to date. Beta-lactones have served as chemical tools manipulate several organisms; however, their potency, selectivity stability limited. Despite detailed structural insights into composition conformational...
Membrane compartmentalization and growth are central aspects of living cells, thus encoded in every cell's genome. For the creation artificial cellular systems, genetic information production membrane building blocks will need to be coupled a similar manner. However, natural biochemical reaction networks notoriously difficult implement vitro. Here, we utilized amphiphilic elastin-like peptides (ELP) create self-assembled vesicular structures about 200 nm diameter. In order genetically encode...
Abstract Caseinolytic protease P (ClpP) is an important regulator of Staphylococcus aureus pathogenesis. A high‐throughput screening for inhibitors ClpP peptidase activity led to the identification first non‐covalent binder this enzyme class. Co‐crystallization small molecule with S. revealed a novel binding mode: Because rotation conserved residue proline 125, locked in defined conformational state, which results distortion catalytic triad and inhibition activity. Based on these structural...
To expedite functional studies of human ClpP we introduce tailored small molecule inhibitors. These compounds are active against the proteolytic ClpXP complex. Target identification elucidates anti-proliferative effects cancer cells.
Abstract Die caseinolytische Protease P ist ein wichtiger Regulator der Pathogenität von Staphylococcus aureus. Mithilfe eines Hochdurchsatz‐Screenings bezüglich Inhibition ClpP‐Peptidaseaktivität identifizierten wir den ersten nichtkovalenten Inhibitor dieser Enzymklasse. Cokristallisation niedermolekularen Verbindung mit ClpP S. aureus offenbarte einen neuen Bindungsmodus: Rotation des konservierten Prolinrests 125 arretiert in einer Konformation, die korrekte Ausrichtung katalytischen...
Phosphoaspartate (pAsp) is a labile posttranslational modification involved in bacterial signaling. To monitor pAsp we designed chemical proteomics method and revealed insights into the antimicrobial response triggered by human peptide hormone.
Triclocarban (TCC), a formerly used disinfectant, kills bacteria via an unknown mechanism of action. A structural hallmark is its N,N'-diaryl urea motif, which also present in other antibiotics, including the recently reported small molecule PK150. We show here that, like PK150, TCC exhibits inhibitory effect on Staphylococcus aureus menaquinone metabolism inhibition biosynthesis protein demethylmenaquinone methyltransferase (MenG). However, activity spectrum (MIC90) across broad range...
Abstract The human mitochondrial ClpXP protease complex (HsClpXP) has recently attracted major attention as a target for novel anti-cancer therapies. Despite its important role in disease progression, the cellular of HsClpXP is poorly characterized and only few small molecule inhibitors have been reported. Herein, we screened previously established S. aureus against related identified potent molecules ClpXP. hit compounds showed activity panoply leukemia, liver breast cancer cell lines. We...
Pseudomonas aeruginosa is a difficult-to-treat Gram-negative bacterial pathogen causing life-threatening infections. Adaptive resistance (AR) to cationic peptide antibiotics such as polymyxin B impairs the therapeutic success. This self-protection mediated by two component systems (TCS) consisting of membrane-bound histidine kinase and an intracellular response regulator (RR). As phosphorylation key RR aspartate residue transient during signaling hydrolytically unstable, study these...
Compartmentalization of biochemical reactions is a central aspect synthetic cells. For this purpose, peptide-based reaction compartments serve as an attractive alternative to liposomes or fatty acid-based vesicles. Externally within the vesicles, peptides can be easily expressed and simplify synthesis membrane precursors. Provided here protocol for creation vesicles with diameters ~200 nm based on amphiphilic elastin-like polypeptides (ELP) utilizing dehydration-rehydration from glass beads....
Compartmentalization of biochemical reactions is a central aspect synthetic cells. For this purpose, peptide-based reaction compartments serve as an attractive alternative to liposomes or fatty acid-based vesicles. Externally within the vesicles, peptides can be easily expressed and simplify synthesis membrane precursors. Provided here protocol for creation vesicles with diameters ~200 nm based on amphiphilic elastin-like polypeptides (ELP) utilizing dehydration-rehydration from glass beads....
Pseudomonas aeruginosa is a difficult-to-treat Gram-negative bacterial pathogen causing life-threatening infections. Adaptive resistance (AR) to cationic peptide antibiotics such as polymyxin B impairs the therapeutic success. This self-protection mediated by two component systems (TCS) consisting of membrane-bound histidine kinase and an intracellular response regulator (RR). As phosphorylation key RR aspartate residue transient during signaling hydrolytically unstable, study these...