A5059066843- Microbial Natural Products and Biosynthesis
- Protein Structure and Dynamics
- Antimicrobial Peptides and Activities
- Biochemical and Structural Characterization
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Antibiotic Resistance in Bacteria
- Advanced NMR Techniques and Applications
- Antimicrobial Resistance in Staphylococcus
- Molecular spectroscopy and chirality
- Bacteriophages and microbial interactions
- Lipid Membrane Structure and Behavior
- Machine Learning in Bioinformatics
- Enzyme Structure and Function
- RNA Research and Splicing
- Monoclonal and Polyclonal Antibodies Research
- Toxin Mechanisms and Immunotoxins
- Chemical Synthesis and Analysis
- Synthesis of β-Lactam Compounds
- Silymarin and Mushroom Poisoning
- Reinforcement Learning in Robotics
- Analytical Chemistry and Chromatography
- Genomics and Chromatin Dynamics
- Glycosylation and Glycoproteins Research
- Antimicrobial agents and applications
Technische Universität Berlin
2021-2025
MSB Medical School Berlin
2024
University of Warwick
2017-2021
VIB-VUB Center for Structural Biology
2012-2020
Coventry (United Kingdom)
2018
University of Graz
2010-2017
Vlaams Instituut voor Biotechnologie
2014-2017
Vrije Universiteit Brussel
2013-2016
European Molecular Biology Laboratory
2013
European Molecular Biology Laboratory
2013
The goal of pE-DB (http://pedb.vib.be) is to serve as an openly accessible database for the deposition structural ensembles intrinsically disordered proteins (IDPs) and denatured based on nuclear magnetic resonance spectroscopy, small-angle X-ray scattering other data measured in solution. Owing inherent flexibility IDPs, solution techniques are particularly appropriate characterizing their biophysical properties, agreement with these provide a convenient tool describing underlying...
Abstract The multi-domain transcriptional coactivators CBP/p300 integrate a multitude of signaling inputs, interacting with more than 400 proteins via one or their globular domains. While function is typically considered in terms these structured domains, about half the protein consists intrinsically disordered regions (IDRs) varying length. However, IDRs have only been thought as linkers that allow flexible spatial arrangement but recent studies shown similar mediate specific and critical...
Antibiotic resistance is a continuously increasing concern for public healthcare. Understanding mechanisms and their emergence crucial the development of new antibiotics effective use. The peptide antibiotic albicidin such promising candidate that, as gyrase poison, shows bactericidal activity against wide range gram-positive gram-negative bacteria. Here, we report discovery gene amplification–based mechanism that imparts an up to 1000-fold increase in levels albicidin. RNA sequencing...
Solid-state NMR is becoming a viable alternative for obtaining information about structures and dynamics of large biomolecular complexes, including ones that are not accessible to other high-resolution biophysical techniques. In this context, methods probing protein-protein interfaces at atomic resolution highly desirable. Solvent paramagnetic relaxation enhancements (sPREs) proved be powerful method in complexes solution but have been employed toward goal the solid state. We demonstrate 1H...
Cyanobacteria frequently form mass developments in surface waters. Populations consist of strains that differ the production bioactive peptides, e.g. microcystins (MC) inhibiting protein phosphatases 1 and 2A anabaenopeptins (APN) carboxypeptidases. Forty-nine (18 green-pigmented (phycocyanin-rich) P. agardhii 31 red-pigmented (phycoerythrin-rich) rubescens strains) filamentous cyanobacterium Planktothrix (Anagnostidis et Komarék) were analysed for their MC APN net rates. These rates...
The bottromycins belong to the ribosomally synthesized and posttranslationally modified peptide (RiPP) family of natural products. Bottromycins exhibit unique structural features, including a hallmark macrolactamidine ring thiazole heterocycle for which divergent members YcaO superfamily have been biosynthetically implicated. Here we report in vitro reconstitution two proteins, BmbD BmbE, responsible ATP-dependent cyclodehydration reactions that yield thiazoline-...
Abstract Solid state NMR is a powerful method to obtain information on the structure and dynamics of protein complexes that, due solubility size limitations, cannot be achieved by other methods. Here, we present an approach that allows quantification microsecond conformational exchange in large using paramagnetic agent accelerate 15 N R 1ρ relaxation dispersion measurements overcome sensitivity limitations. The validated crystalline GB1 then applied >300 kDa precipitated complex with full...
The peptide albicidin represents a highly promising lead structure which is first-in-class antibiotic with remarkable potency against gram-negative bacteria. Past efforts in the synthesis of analogs focused on increasing hydrophilicity, broadening antibacterial profile and overcoming resistance. Herein, we present synthetic derivatives variations N-terminal building block characterize their activity DNA gyrase inhibition. Furthermore, show that N-terminus greatly affects binding to...
The par toxin−antitoxin system is required for the stable inheritance of plasmid pAD1 in its native host Enterococcus faecalis. It codes toxin Fst and a small antisense RNA which inhibits translation mRNA, it only known regulated Gram-positive bacteria. This study presents structure Fst, first atomic resolution component an system. mode membrane binding was determined by relaxation enhancements paramagnetic environment molecular dynamics simulation. forms membrane-binding α-helix N-terminal...
Interactions of macrolide antibiotics with biological membranes contribute to their bioavailability but are also involved in the formation phospholipidosis, which is caused by inhibition phospholipase A(1) activity. We determined interaction strength and localization membrane-mimetics. Macrolides bind membrane-mimetics positively charged amino groups being close micelle surface thereby protect lipids from degraded rather than inhibiting enzyme.
Abstract The enoyl‐acyl carrier protein reductase enzyme FabI is essential for fatty acid biosynthesis in Staphylococcus aureus and represents a promising target the development of novel, urgently needed anti‐staphylococcal agents. Here, we elucidate mode action kalimantacin antibiotics, novel class inhibitors with clinically‐relevant activity against multidrug‐resistant S. . By combining X‐ray crystallography molecular dynamics simulations, vitro kinetic studies chemical derivatization...
Nonribosomal peptides are a structurally diverse and bioactive class of natural products constructed by multidomain enzymatic assembly lines known as nonribosomal peptide synthetases (NRPSs). While the core catalytic domains even entire protein subunits NRPSs have been elucidated, little biophysical work has reported on docking that promote interactions—and thus transfer biosynthetic intermediates—between subunits. In present study, we closely examine COM mediate COMmunication between donor...
The peptide hormone ghrelin, which is the natural ligand of membrane-bound growth secretagogue receptor (GHS-R), regulates overall body and cell growth, energy homeostasis, carbohydrate, protein lipid metabolism water electrolyte balance. It contains an O-acyl linked octanoyl group on Ser3 only known to contain such a modification. Using solution state NMR spectroscopy ultrafiltration we found that human ghrelin binds membrane-mimetic environments via its as well aromatic moiety Phe4....
Synonymous constraint elements (SCEs) are protein-coding genomic regions with very low synonymous mutation rates believed to carry additional, overlapping functions. Thousands of such potentially multi-functional were recently discovered by analyzing the levels and patterns evolutionary conservation in human coding exons. These provide a good opportunity improve our understanding how redundant nature genetic code is exploited cell. Our premise that protein segments encoded might better...
Synthetic methods on the macrocyclization of peptides are high interest since they facilitate synthesis various types potentially bioactive compounds, e.g. addressing targets like protein–protein-interactions. Herein, we report an efficient method to construct tryptathionine-cross-links in between amino acids Trp and Cys. This reaction not only is basis for total death cap toxin α-amanitin but also provides rapid access new amanitin analogues. study first time presents a systematic...
α-Amanitin is a bicyclic octapeptide composed of macrolactam with tryptathionine cross-link forming handle. Previously, the occurrence isomers amanitin, termed atropisomers has been postulated. Although total synthesis α-amanitin accomplished this aspect still remains unsolved. We perform amanitin analogs, accompanied by in-depth spectroscopic, crystallographic and molecular dynamics studies. The data unambiguously confirms two amatoxin-type isomers, for which we propose term ansamers....
Indolic derivatives can affect fibril growth of amyloid forming proteins. The neurotransmitter serotonin (5-HT) is particular interest, as it an endogenous molecule with a possible link to neuropsychiatric symptoms Parkinson disease. A key pathomolecular mechanism disease the misfolding and aggregation intrinsically unstructured protein α-synuclein. We performed biophysical study investigate influence between these two molecules. In isolated in vitro system, 5-HT interfered α-synuclein fiber...