A5067914218- Plant biochemistry and biosynthesis
- Polysaccharides and Plant Cell Walls
- Microbial Natural Products and Biosynthesis
- Plant Reproductive Biology
- Plant Molecular Biology Research
- Photodynamic Therapy Research Studies
- Computational Drug Discovery Methods
- Nanoplatforms for cancer theranostics
- X-ray Diffraction in Crystallography
- Immunotherapy and Immune Responses
- Enzyme Structure and Function
- Crystallization and Solubility Studies
- Natural product bioactivities and synthesis
- Microbial Metabolic Engineering and Bioproduction
- RNA and protein synthesis mechanisms
- Soybean genetics and cultivation
- Biochemical and Molecular Research
- Photosynthetic Processes and Mechanisms
- Food Quality and Safety Studies
- Bladder and Urothelial Cancer Treatments
- Trypanosoma species research and implications
- Bacterial Genetics and Biotechnology
- Yersinia bacterium, plague, ectoparasites research
- Lipid Membrane Structure and Behavior
- Botanical Research and Chemistry
University of Freiburg
2021-2024
Technical University of Munich
2006-2010
Center for Integrated Protein Science Munich
2008
The extracellular matrix plays an integrative role in cellular responses plants, but its contribution to the signalling of ligands largely remains be explored. Rapid alkalinisation factors (RALFs) are peptide hormones that play pivotal roles various physiological processes. Here, we address a crucial connection between de-methylesterification machinery cell wall component pectin and RALF1 activity. Pectin is polysaccharide, contributing structural integrity wall. Our data illustrate...
Abstract A library of 40 000 compounds was screened for inhibitors 2‐methylerythritol 2,4‐cyclodiphosphate synthase (IspF) protein from Arabidopsis thaliana using a photometric assay. thiazolopyrimidine derivative resulting the high‐throughput screen found to inhibit IspF proteins Mycobacterium tuberculosis , Plasmodium falciparum and A. with IC 50 values in micromolar range. Synthetic efforts afforded derivatives that M. P. low Several act as weak red blood cell
Protein modification by interferon-stimulated gene 15 (ISG15), termed ISGylation, exhibits antiviral properties and influences tumorigenesis, genome stability metabolic processes. ISGylation is counteracted the specific protease USP18. Likewise, viral proteases such as papain-like (PLpro) from SARS-CoV-2 cleave ISG15 to undermine host immune response. Beyond its role a deISGylating enzyme, USP18 acts major negative regulator of IFN signaling pathway in STAT2-dependent manner. In humans,...
IspE kinase inhibitors. The first inhibitors for the IspE, an enzyme of non-mevalonate pathway, are presented. nonphosphate based avoid binding to ATP site but instead occupy substrate and a small, newly detected hydrophobic subpocket at active IspE. With appropriate filling this pocket, competitive inhibition constants Kic in upper nanomolar range measured.
Enzymes of the non-mevalonate pathway for isoprenoid biosynthesis are therapeutic targets treatment important infectious diseases. Whereas this is absent in humans, it used by plants, many eubacteria and apicomplexan protozoa, including major human pathogens such as Plasmodium falciparum Mycobacterium tuberculosis. Herein, we report on design, preparation biological evaluation a new series ligands IspE protein, kinase from pathway. These inhibitors were developed inhibition Escherichia coli,...
The ispC gene of Arabidopsis thaliana was expressed in pseudomature form without the putative plastid-targeting sequence a recombinant Escherichia coli strain. protein purified by affinity chromatography and shown to catalyze formation 2C-methyl-D-erythritol 4-phosphate from 1-deoxy-D-xylulose 5-phosphate at rate 5.6 micromol x min(-1) mg(-1) (k(cat) 4.4 s(-1)). Michaelis constants for cosubstrate NADPH are 132 30 microm, respectively. enzyme has an absolute requirement divalent metal ions,...
Designed inhibitors (like 1) of IspF, a key enzyme in the non-mevalonate pathway for terpene biosynthesis and potential antimalarial target, were synthesized evaluated. Since fluorescent probes introduced these ligands, their affinity towards IspF from E. coli could be determined by fluorescence titrations. The binding modes two ligands ternary complexes with ZnII ion clarified X-ray analysis.
4‐Diphosphocytidyl‐2 C ‐methyl‐ d ‐erythritol kinase (IspE) catalyses the ATP‐dependent conversion of 4‐diphosphocytidyl‐2 (CDPME) to 2‐phosphate with release ADP. This reaction occurs in non‐mevalonate pathway isoprenoid precursor biosynthesis and because it is essential important microbial pathogens absent from mammals represents a potential target for anti‐infective drugs. We set out characterize biochemical properties, determinants molecular recognition reactivity IspE report cloning...
Abstract The enzymes of the non‐mevalonate pathway for isoprenoid biosynthesis are attractive targets development novel drugs against malaria and tuberculosis. This is used exclusively by corresponding pathogens, but not humans. A series water‐soluble, cytidine‐based inhibitors that were originally designed fourth enzyme in pathway, IspD, shown to inhibit subsequent enzyme, kinase IspE (from Escherichia coli ). binding mode was verified co‐crystal structure analysis, using Aquifex aeolicus...
Abstract In this paper, we describe the structure‐based design, synthesis, and biological evaluation of cytosine derivatives analogues that inhibit IspF, an enzyme in non‐mevalonate pathway isoprenoid biosynthesis. This is responsible for biosynthesis C 5 precursors to isoprenoids, isopentenyl diphosphate (IPP, 1 ) dimethylallyl (DMAPP, 2 ; Scheme ). The sole source protozoan Plasmodium parasites. Since mammals exclusively utilize alternative mevalonate pathway, enzymes have been identified...
Pathogenic yersiniae utilize a type three secretion system (T3SS) to inject Yop proteins into host cells in order undermine their immune response. YscM1 and YscM2 have been reported be functionally equivalent regulators of the T3SS Yersinia enterocolitica. Here, we show by affinity purification, native gel electrophoresis small angle x-ray scattering that both bind phosphoenolpyruvate carboxylase (PEPC) Y. Under vitro conditions, YscM1, but not YscM2, was found inhibit PEPC with an apparent...
The extracellular matrix plays an integrative role in cellular responses plants, but its contribution to the signalling of ligands largely remains be explored. RAPID ALKALINIZATION FACTORs (RALFs) are peptide hormones that play pivotal roles various physiological processes. Here, we address a crucial connection between demethylation machinery cell wall component pectin and RALF1 activity. Pectin is polysaccharide, contributing structural integrity wall. Our data illustrate pharmacological...
The extracellular matrix plays an integrative role in cellular responses plants, but its contribution to the signalling of ligands largely remains be explored. Rapid alkalinisation factors (RALFs) are peptide hormones that play pivotal roles various physiological processes. Here, we address a crucial connection between de-methylesterification machinery cell wall component pectin and RALF1 activity. Pectin is polysaccharide, contributing structural integrity wall. Our data illustrate...
2 C ‐Methyl‐ d ‐erythritol‐4‐phosphate synthase, encoded by the isp gene (also designated dxr ), catalyzes first committed step in nonmevalonate isoprenoid biosynthetic pathway. The reaction involves isomerization of 1‐deoxy‐ ‐xylulose 5‐phosphate, giving a branched‐chain aldose derivative that is subsequently reduced to ‐methyl‐ ‐erythritol 4‐phosphate. has been proposed proceed as an intramolecular rearrangement or retroaldol–aldol sequence. We report preparation 13 C‐labeled substrate...
Photoimmunotherapy (PIT) combines the specificity of antibodies with cytotoxicity light activatable photosensitizers (PS) and is a promising new cancer therapy. We designed synthesized, in highly convergent manner, silicon phthalocyanine dye WB692-CB2, which novel for being first light-activatable PS that can be directly conjugated via maleimide linker to cysteines. In present study we WB692-CB2 humanized antibody engineered cysteines heavy chains specifically targets prostate-specific...
Strukturbasiert entworfene Hemmstoffe (wie 1) von IspF, einem Schlüsselenzym im „Nicht-Mevalonat-Weg“ der Terpenbiosynthese, wurden synthetisiert und auf ihre biologische Aktivität untersucht. Ihre Affinität gegen IspF aus E. coli wurde durch Fluoreszenztitration bestimmt. Der röntgenographisch ermittelte Bindungsmodus zwei Liganden in Komplexen mit ZnII-Ion liefert Erkenntnisse für die Entwicklung niedermolekularer, Wirkstoff-ähnlicher Hemmstoffe.
Abstract The extracellular matrix plays an integrative role in cellular responses plants, but its contribution to the signalling of ligands largely remains be explored. RAPID ALKALINIZATION FACTORs (RALFs) are peptide hormones that play pivotal roles various physiological processes. Here, we address a crucial connection between de-methylesterification machinery cell wall component pectin and RALF1 activity. Pectin is polysaccharide, contributing structural integrity wall. Our data illustrate...
Background/Aim: Although there are curative treatment options for non-muscle-invasive bladder cancer, the recurrence of this tumor is high. Therefore, novel targeted therapies needed complete removal cancer cells in stages localized disease, order to avoid local recurrence, spare patients from stressful and expensive procedures increase their quality life expectancy. This study tested a new approach photoimmunotherapy (PIT) cancer. Materials Methods: We generated cysteine modified...
The standard treatment for localized prostate cancer involves surgical removal of the with curative intent. However, when tumor cells persist in operation site, there is high risk local recurrence and spread, leading to stressful follow-up treatments, impaired quality life, reduced overall survival. This study examined photoimmunotherapy (PIT) as a new option cells.
Background/Aim: Breast cancer (BC) is the most common malignant disease worldwide. Localized stages of BC can be successfully treated by surgery. However, local recurrence occurs in about 4-10% patients, requiring systemic treatments that impair patients' quality life and shortens expectancy. Therefore, new therapeutic options are needed, which used intraoperatively contribute to complete removal residual tumor cells surgical area. In present study, we describe a cysteine-modified variant...
The extracellular matrix plays an integrative role in cellular responses plants, but its contribution to the signalling of ligands largely remains be explored. RAPID ALKALINIZATION FACTORs (RALFs) are peptide hormones that play pivotal roles various physiological processes. Here, we address a crucial connection between de-methylesterification machinery cell wall component pectin and RALF1 activity. Pectin is polysaccharide, contributing structural integrity wall. Our data illustrate...