A5051796734- PARP inhibition in cancer therapy
- Toxin Mechanisms and Immunotoxins
- RNA modifications and cancer
- Calcium signaling and nucleotide metabolism
- DNA Repair Mechanisms
- Protein Structure and Dynamics
- Biochemical and Molecular Research
- Enzyme Structure and Function
- RNA Research and Splicing
- Genetic Neurodegenerative Diseases
RWTH Aachen University
2021-2025
University Hospital Bonn
2024
Boehringer Ingelheim (Germany)
2020
Abstract RNA function relies heavily on posttranscriptional modifications. Recently, it was shown that certain PARPs and TRPT1 can ADP-ribosylate in vitro. Traditionally, intracellular ADP-ribosylation has been considered mainly as a protein posttranslational modification. To date, is not clear whether occurs cells. Here we present evidence different species are ADP-ribosylated human The modification of cellular mediated by several transferases such TRPT1, PARP10, PARP11, PARP12 PARP15...
Abstract ADP-ribosylation is well-known as protein posttranslational modification and was recently also identified RNA posttranscriptional modification. When macrodomain proteins were ADP-ribosylhydrolases, several substrates not yet identified. Therefore, the majority of macrodomain-containing have been tested towards these additional considered to be inactive. Here, we compare in vitro activities human macrodomains on a range ADP-ribosylated substrates. We confirm recent findings that...
The modification of substrates with ADP-ribose (ADPr) is important in, for example, antiviral immunity and cancer. Recently, several reagents were developed to detect ADP-ribosylation; however, it unknown whether they recognise ADPr, specific amino acid–ADPr linkages, or ADPr the surrounding protein backbone. We first optimised methods prepare extracts containing ADPr–proteins observe that depending on acid modified, heatlabile. tested reactivity available diverse ADP-ribosylated RNA...
Significance We present a comprehensive structural study, which shows the human GCH1 and GCH1−GFRP complexes in all states (apo, ligand bound, partially fully inhibited). observed local rearrangements allosteric pocket upon BH4 binding, result drastic changes quaternary structure of enzyme leading to more compact, tense form inhibited protein. Inhibition enzymatic activity is not hindrance substrate but rather consequence accelerated binding kinetics as shown by STD-NMR site-directed...
<title>Abstract</title> ADP-ribosylation is well-known as protein posttranslational modification and was recently also identified RNA posttranscriptional modification. ADP-ribose added onto substrates by PARP enzymes removed the structurally distinct ADP-ribosylhydrolases (ARH) or macrodomain-containing proteins. When macrodomain proteins were hydrolases a decade ago, many not yet identified. Therefore, majority of have been tested towards these additional considered to be inactive. Here, we...
Recent evidence suggests that modification of substrates with a single ADP-ribose (ADPr) is important in for example antiviral immunity and cancer. However, the endogenous extent mono-ADP-ribosylation are still largely unclear. Several reagents were developed to detect ADP-ribosylation but it unknown whether they recognise only ADPr, amino acid-ADPr linkages or combination ADPr protein backbone. We screened affinity selected enzymatically, chemically cell generated on glutamate, cysteine,...