- Enzyme Structure and Function
- Bacterial Genetics and Biotechnology
- Metal complexes synthesis and properties
- Antibiotic Resistance in Bacteria
- Peptidase Inhibition and Analysis
- SARS-CoV-2 and COVID-19 Research
- Radiopharmaceutical Chemistry and Applications
- Metal-Catalyzed Oxygenation Mechanisms
- Cancer therapeutics and mechanisms
- Magnetism in coordination complexes
- Amino Acid Enzymes and Metabolism
- RNA and protein synthesis mechanisms
- Carbohydrate Chemistry and Synthesis
- Enzyme Production and Characterization
- Computational Drug Discovery Methods
- Bacteriophages and microbial interactions
- Photosynthetic Processes and Mechanisms
- Protein Structure and Dynamics
- Organometallic Complex Synthesis and Catalysis
- Chemical Reactions and Isotopes
- Chemical Synthesis and Analysis
- Lanthanide and Transition Metal Complexes
- DNA and Nucleic Acid Chemistry
- Antimicrobial Peptides and Activities
- Microbial bioremediation and biosurfactants
Universität Greifswald
2014-2024
Universität Hamburg
1982-2021
Universitätsmedizin Greifswald
2021
University of Cambridge
2012
Wellcome Trust
2012
Bruker (Germany)
2010
Osaka University
2010
Albert Einstein College of Medicine
2010
Freie Universität Berlin
1989-2000
Leibniz Institute for Crystal Growth
2000
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...
The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug available to directly treat the disease. In a search for against COVID-19, we have performed high-throughput x-ray crystallographic screen of two repurposing libraries main protease (M
The fungal proteinase K (EC 3.4.21.14) is a very potent unusually stable member of the subtilisin family. Its X-ray structure determined at 0.15-nm resolution shows two bound Ca2+ ions. Ca1 in near-ideal pentagonal bipyramidal configuration with Asp200 carboxylate and Pro175 peptide C = O an apical, Val177 four water molecules equatorial position, whereas Ca2 displays incomplete octahedral coordination Asp260, Val16 molecules. Scatchard analysis titration Ca2+-free yields single dissociation...
The flavin-dependent monooxygenase TetX confers resistance to all clinically relevant tetracyclines, including the recently approved, broad-spectrum antibiotic tigecycline (Tygacil®) which is a critical last-ditch defense against multidrug-resistant pathogens. represents first mechanism tigecycline, circumvents both tet-gene encoded resistances, relying on active efflux of and ribosomal protection proteins. alternative enzyme-based depends regioselective hydroxylation tetracycline...
SARS-CoV-2 papain-like protease (PLpro) covers multiple functions. Beside the cysteine-protease activity, facilitating cleavage of viral polypeptide chain, PLpro has additional and vital function removing ubiquitin ISG15 (Interferon-stimulated gene 15) from host-cell proteins to support coronaviruses in evading host's innate immune responses. We identified three phenolic compounds bound PLpro, preventing essential molecular interactions by screening a natural compound library. The X-ray...
The excessive use of antibiotics has enabled bacteria to develop resistance through a variety mechanisms. most common bacteriostatic action the broad-spectrum antibiotic tetracycline (Tc) is by inactivation bacterial ribosome so that protein biosynthesis interrupted and die. mechanism in gram-negative against Tc associated with membrane-intrinsic TetA, which exports invaded out cell before it can attack its target, ribosome. expression TetA tightly regulated homodimeric Tet repressor...
In the crystal structure of polyiodide complex (p-nitrophenyl-alpha-maltohexaose(2)) . Ba(I(3))(2) 22H(2)O, maltohexaose units form an antiparallel, left-handed double helix with O-2 ... O-3 and O-6 hydrogen bonding a central cavity that encloses two triiodide units. This contrasts parallel, no proposed for A-and B-starch single in V-amylose may be relevant stabilization glycogen Structure.
Abstract Flavonoids are a large group of plant secondary metabolites with variety biological properties and therefore interest to many scientists, as they can lead industrially interesting intermediates. The anaerobic gut bacterium Eubacterium ramulus catabolize flavonoids, but until now, the pathway has not been experimentally confirmed. In present work, chalcone isomerase (CHI) an enoate reductase (ERED) could be identified through whole genome sequencing gene motif search. These two...
Bacillus subtilis encodes redox-sensing MarR-type regulators of the OhrR and DUF24-families that sense organic hydroperoxides, diamide, quinones or aldehydes via thiol-based redox-switches. In this article, we characterize novel MarR/DUF24-family regulator HypR (YybR) is activated by disulphide stress caused diamide NaOCl in B. subtilis. controls positively a flavin oxidoreductase HypO confers protection against stress. The conserved N-terminal Cys14 residue has lower pKa 6.36 essential for...
Emerging RNA viruses, including SARS-CoV-2, continue to be a major threat. Cell entry of SARS-CoV-2 particles via the endosomal pathway involves cysteine cathepsins. Due ubiquitous expression, cathepsin L (CatL) is considered promising drug target in context different viral and lysosome-related diseases. We characterized anti-SARS-CoV-2 activity set carbonyl- succinyl epoxide-based inhibitors, which were previously identified as inhibitors cathepsins or related proteases. Calpain inhibitor...
Abstract A new type of crystals the reaction center I complex, RC I, water splitting photosynthesis has been prepared from cyanobacterium Synechococcus sp. In contrast to our first (11), ones have a length up 1 mm, thickness 50 μm and show X‐ray diffraction patterns with resolution about 4 Å. The space group hexagonal is probably P6 3 22. One represents asymmetric unit. unit cell dimensions are = b 285 Å, c 167 α β 90° γ 120°. building block crystal lattice trimer (diameter ˜19 nm, height ˜6...
Fluorescently labeled cobalt peptide deformylase (Co-PDF) can be efficiently used as a fluorescence-resonance-energy-transfer-based sensing device for hydrogen sulfide (H2S). The proof of concept our sensor system is substantiated by spectroscopic, structural, and theoretical results. Monohydrogen coordination to Co-PDF Ni-PDF was verified X-ray crystallography. Density functional theory calculations were performed gain insight into the characteristics adduct between H2S cofactor in Co-PDF.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTVariable-temperature single-crystal electron spin resonance study and crystal structure of bis(1,4,7-triazacyclononane)copper(2+) tricyanocuprate(2-) dihydrate at 110 293 K. Static dynamic Jahn-Teller distortions in the CuN6 polyhedronPhalguni Chaudhuri, Karen Oder, Karl Wieghardt, Johannes Weiss, Jan Reedijk, Winfried Hinrichs, John Wood, Andrej Ozarowski, Horst Stratemaier, Dirk ReinenCite this: Inorg. Chem. 1986, 25, 17, 2951–2958Publication...
The importance of amine transaminases for producing optically pure chiral precursors pharmaceuticals and chemicals has substantially increased in recent years. X-ray crystal structure the (R)-selective transaminase from fungus Aspergillus fumigatus was solved by S-SAD phasing to 1.84 Å resolution. refined at 1.27 resolution provides detailed knowledge about molecular basis substrate recognition conversion facilitate protein-engineering approaches. protein forms a homodimer belongs fold class...
Chiral amines are important precursors for the pharmaceutical and fine-chemical industries. Because of this, demand enantiopure is currently increasing. Amine transaminases can produce a large spectrum chiral in (R)- or (S)-configuration, depending on their substrate scope stereo-preference, by converting prochiral ketone into amine while using alanine as donor producing pyruvate an α-keto acid product. In order to guide protein engineering improve specificity enantioselectivity, we carried...
Several drug screening campaigns identified Calpeptin as a candidate against SARS-CoV-2. Initially reported to target the viral main protease (Mpro), its moderate activity in Mpro inhibition assays hints at second target. Indeed, we show that is an extremely potent cysteine cathepsin inhibitor, finding additionally supported by X-ray crystallography. Cell infection proved Calpeptin's efficacy Treatment of SARS-CoV-2-infected Golden Syrian hamsters with sulfonated dose 1 mg/kg body weight...