A5029478690- DNA Repair Mechanisms
- Enzyme Structure and Function
- DNA and Nucleic Acid Chemistry
- Metalloenzymes and iron-sulfur proteins
- Tuberculosis Research and Epidemiology
- Bacterial Genetics and Biotechnology
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Biochemical and Molecular Research
- Ubiquitin and proteasome pathways
- CRISPR and Genetic Engineering
- Porphyrin Metabolism and Disorders
- Antibiotic Resistance in Bacteria
- Computational Drug Discovery Methods
- Genomics and Chromatin Dynamics
- Enzyme function and inhibition
- Microbial Natural Products and Biosynthesis
- Antimicrobial agents and applications
- Cancer therapeutics and mechanisms
- Metal-Catalyzed Oxygenation Mechanisms
- Advanced biosensing and bioanalysis techniques
- Reproductive tract infections research
- Chemical Synthesis and Analysis
- Polyamine Metabolism and Applications
- Electrocatalysts for Energy Conversion
University of Würzburg
2015-2025
Stony Brook University
2000-2021
University of Zurich
2021
TU Dortmund University
2021
Columbia University
2021
Comprehensive Cancer Center Mainfranken
2014-2020
Universitätsklinikum Würzburg
2020
Centre Virchow-Villermé
2016
Deutsche Forschungsgemeinschaft
2014
Institut de Biologie Moléculaire et Cellulaire
2014
The molybdoenzyme dimethylsulfoxide (DMSO) reductase contributes to the release of dimethylsulfide, a compound that has been implicated in cloud nucleation and global climate regulation. crystal structure DMSO from Rhodobacter sphaeroides reveals monooxo molybdenum cofactor containing two molybdopterin guanine dinucleotides asymmetrically coordinate through their dithiolene groups. One pterins exhibits different coordination modes between oxidized reduced states, whereas side chain oxygen...
Protein-protein interactions play critical roles in biology, but the structures of many eukaryotic protein complexes are unknown, and there likely not yet identified. We take advantage advances proteome-wide amino acid coevolution analysis deep-learning–based structure modeling to systematically identify build accurate models core within
The most frequently occurring resistance of Gram-negative bacteria against tetracyclines is triggered by drug recognition the Tet repressor. This causes dissociation repressor-operator DNA complex and enables expression protein TetA, which responsible for active efflux tetracycline. 2.5 angstrom resolution crystal structure homodimeric repressor complexed with tetracycline-magnesium reveals detailed recognition. orientation operator-binding helix-turn-helix motifs inverted in comparison...
Corticotropin-independent Cushing's syndrome is caused by tumors or hyperplasia of the adrenal cortex. The molecular pathogenesis cortisol-producing adenomas not well understood.
Novel chemotherapeutics for treating multidrug-resistant (MDR) strains of Mycobacterium tuberculosis (MTB) are required to combat the spread tuberculosis, a disease that kills more than 2 million people annually. Using structure-based drug design, we have developed series alkyl diphenyl ethers uncompetitive inhibitors InhA, enoyl reductase enzyme in MTB fatty acid biosynthesis pathway. The most potent compound has Ki' value 1 nM InhA and MIC99 values 2-3 microg mL(-1) (6-10 microM) both...
DNA damage recognition by the nucleotide excision repair pathway requires an initial step identifying helical distortions in and a proofreading verifying presence of lesion. This is accomplished eukaryotes TFIIH complex. The critical component XPD protein, helicase that unwinds identifies damage. Here, we describe crystal structure archaeal protein with high sequence identity to human reveals how structural framework combined additional elements for strand separation scanning. Two RecA-like...
Mitochondrial DNA polymerase gamma (pol gamma) is responsible for replication and repair of mtDNA mutated in individuals with genetic disorders such as chronic external ophthalmoplegia Alpers syndrome. pol also an adventitious target toxic side effects several antiviral compounds, mutation its proofreading exonuclease leads to accelerated aging mouse models. We have used a variety physical functional approaches study the interaction human catalytic subunit both wild-type accessory factor,...
Enhanced expression of the MYC transcription factor is observed in majority tumors. Two seemingly conflicting models have been proposed for its function: one proposes that enhances all genes, while other model suggests gene-specific regulation. Here, we explored hypothesis specific gene profiles arise since promoters differ affinity and high-affinity are fully occupied by physiological levels MYC. We determined cellular used RNA- ChIP-sequencing to correlate promoter occupancy with at...
G-quadruplex (G4) DNA, an alternate structure formed by Hoogsteen hydrogen bonds between guanines in G-rich sequences, threatens genomic stability perturbing normal DNA transactions including replication, repair, and transcription. A variety of G4 topologies (intra- intermolecular) can form vitro, but the molecular architecture cellular factors influencing landscape vivo are not clear. Helicases that unwind structured molecules emerging as important class G4-resolving enzymes. The...
Somatic mutations in PRKACA gene, encoding the catalytic subunit of protein kinase A (PKA), have been recently found a high proportion sporadic adenomas associated with Cushing's syndrome. The aim was to analyze mutation large cohort patients adrenocortical masses. Samples from nine European centers were included (Germany, n = 4; Italy, France, 1). drawn 149 nonsecreting (n 32 + 2 peritumoral), subclinical hypercortisolism 36), syndrome 64 androgen-producing tumors 4), carcinomas 5 and...
The prototype of the γ-class carbonic anhydrase has been characterized from methanogenic archaeon Methanosarcina thermophila. Previously reported kinetic studies are consistent with this enzyme having a reaction mechanism similar to that mammalian α-class anhydrase. However, overall folds these two enzymes dissimilar, and apart zinc-coordinating histidines, active site residues bear little resemblance one another. crystal structures zinc-containing cobalt-substituted anhydrases M....