A5051982388- Computational Drug Discovery Methods
- SARS-CoV-2 and COVID-19 Research
- Enzyme Structure and Function
- Photosynthetic Processes and Mechanisms
- Protein Structure and Dynamics
- Biochemical and biochemical processes
- Algal biology and biofuel production
- Amino Acid Enzymes and Metabolism
- Peptidase Inhibition and Analysis
- COVID-19 Clinical Research Studies
- Neurological diseases and metabolism
- interferon and immune responses
- Biochemical Acid Research Studies
- Advanced Electron Microscopy Techniques and Applications
- X-ray Spectroscopy and Fluorescence Analysis
- Synthesis and biological activity
- X-ray Diffraction in Crystallography
- Microbial Metabolic Engineering and Bioproduction
- Diverse Scientific Research Studies
- Crystallization and Solubility Studies
- Ubiquitin and proteasome pathways
- CRISPR and Genetic Engineering
- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Phagocytosis and Immune Regulation
Helmholtz-Zentrum Berlin für Materialien und Energie
2017-2024
Helmholtz Centre for Infection Research
2020-2022
University of Würzburg
2016-2020
Center for Free-Electron Laser Science
2020
Universität Hamburg
2020
University of Bayreuth
2017
Cornell University
2013
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
Thermophilic polyester hydrolases (PES-H) have recently enabled biocatalytic recycling of the mass-produced synthetic polyethylene terephthalate (PET), which has found widespread use in packaging and textile industries. The growing demand for efficient PET prompted us to solve high-resolution crystal structures two metagenome-derived enzymes (PES-H1 PES-H2) notably also complex with various substrate analogues. Structural analyses computational modeling using molecular dynamics simulations...
TfCa, a promiscuous carboxylesterase from Thermobifida fusca, was found to hydrolyze polyethylene terephthalate (PET) degradation intermediates such as bis(2-hydroxyethyl) (BHET) and mono-(2-hydroxyethyl)-terephthalate (MHET). In this study, we elucidated the structures of TfCa in its apo form, well complex with PET monomer analogue BHET. The structure-function relationship investigated by comparing hydrolytic activity on various ortho- para-phthalate esters different lengths....
RNA editosomes selectively deaminate cytidines to uridines in plant organellar transcripts-mostly restore protein functionality and consequently facilitate mitochondrial chloroplast function. The editosomal pentatricopeptide repeat proteins serve target recognition, whereas the intensively studied DYW domain elicits catalysis. Here we present structures functional data of a an inactive ground state activated. domains harbour cytidine deaminase fold C-terminal motif, with catalytic structural...
Fast screening of enzyme variants is crucial for tailoring biocatalysts the asymmetric synthesis non-natural chiral chemicals, such as amines. However, most existing methods either are limited by throughput or require specialized equipment. Herein, we report a simple, high-throughput, low-equipment dependent, and generally applicable growth selection system engineering amine-forming converting enzymes apply it to improve belonging three different classes. This results in (i) an amine...
MXCuBE2 is the second-generation evolution of MXCuBE beamline control software, initially developed and used at ESRF – European Synchrotron. extends, in an intuitive graphical user interface (GUI), functionalities data collection methods available to users while keeping all previously features allowing for straightforward incorporation ongoing future developments. introduces extended abstraction layer that allows easy interfacing any kind macromolecular crystallography (MX) hardware...
Protein ubiquitination occurs through the sequential formation and reorganization of specific protein-protein interfaces. Ubiquitin-conjugating (E2) enzymes, such as Ube2S, catalyze an isopeptide linkage between C-terminus a “donor” ubiquitin primary amino group “acceptor” molecule. This reaction involves intermediate, in which donor is thioester-bound to active site cysteine E2 functionally important interface formed two proteins. A docked model Ube2S-donor complex was generated previously,...
Directed evolution can be a powerful tool for revealing the mutational pathways that lead to more resistant bacterial strains. In this study, we focused on bacterium Mycobacterium tuberculosis, which is members of β-lactam class antibiotics and thus continues pose major public health threat. Resistance organism result chromosomally encoded, extended spectrum A β-lactamase, BlaC, constitutively produced. Here, combinatorial enzyme libraries were selected ampicillin identify mutations...
Fragment screening is a technique that helps to identify promising starting points for ligand design. Given crystals of the target protein are available and display reproducibly high-resolution X-ray diffraction properties, crystallography among most preferred methods fragment because its sensitivity. Additionally, it only method providing detailed 3D information binding mode fragment, which vital subsequent rational compound evolution. The routine use depends on availability suitable...
Abstract The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous health problems and economical challenges for mankind. To date, no effective drug available to directly treat the prevent virus spreading. In a search against COVID-19, we have performed massive X-ray crystallographic screen of two repurposing libraries main protease (M pro ), which essential replication and, thus, potent target. contrast commonly applied fragment screening experiments with molecules low...
The HECT-type ubiquitin ligase E6AP (UBE3A) is critically involved in several neurodevelopmental disorders and human papilloma virus-induced cervical tumorigenesis; the structural mechanisms underlying activity of this crucial ligase, however, are incompletely understood. Here, we report a crystal structure C-terminal lobe ("C-lobe") catalytic domain that reveals two molecules domain-swapped, dimeric arrangement. Interestingly, molecular hinge enables reorganization with respect to monomeric...
The carbon cage of buckminsterfullerene Ih -C60 , which obeys the Isolated-Pentagon Rule (IPR), can be transformed to non-IPR cages in course high-temperature chlorination C60 or Cl30 with SbCl5 . chloro derivatives were isolated chromatographically (HPLC) and characterized crystallographically as 1809 Cl16 1810 Cl24 1805 contain, respectively two, four, four pairs fused pentagons cage. High-temperature trifluoromethylation products CF3 I afforded a derivative, 1807 (CF3 )12 contains...
Isovaleryl coenzyme A (IV-CoA) is an important precursor for iso-fatty acids and lipids. It acts in the development of myxobacteria, which can produce this compound from acetyl-CoA through alternative IV-CoA biosynthesis (aib). central reaction aib catalyzed by AibA/AibB, as a cofactor-free decarboxylase despite belonging to family CoA-transferases. We developed efficient expression system AibA/AibB that allowed determination high-resolution crystal structures complex with different ligands....
In the past two decades, most of steps in a macromolecular crystallography experiment have undergone tremendous development with respect to speed, feasibility and increase throughput. The part experimental workflow that is still bottleneck, despite significant efforts, involves manipulation harvesting crystals for diffraction experiment. Here, novel low-cost device presented functions as cover 96-well crystallization plates. This enables access individual experiments one at time by its...
Variable-temperature single-crystal X-ray diffraction elaborated the phase transition in Sc 3 N@C 70 crystals and allowed to distinguish hidden static disorder from dynamic caused by thermal motion.
Fragment screening is a technique that helps to identify promising starting points for ligand design. Given crystals of the target protein are available and display reproducibly high-resolution X-ray diffraction properties, crystallography among most preferred methods fragment because its sensitivity. Additionally, it only method providing detailed 3D information binding mode fragment, which vital subsequent rational compound evolution. The routine use depends on availability suitable...
Native cytochrome c6 was purified from an extract of strain BP-1 the thermophilic cyanobacterium Thermosynechococcus elongatus. The protein crystallized, and with only slight modifications buffer vapour-diffusion conditions two different space groups were observed, namely H3 C2. Both crystal structures solved; they contained three six molecules per asymmetric unit refined to 1.7 2.25 Å resolution, respectively. To date, structure native T. elongatus has been reported as a monomer using NMR...
Abstract Here we present the crystal structure of SARS-CoV-2 main protease (M pro ) covalently bound to 2-methyl-1-tetralone. This complex was obtained by co-crystallization M with HEAT (2-(((4-hydroxyphenethyl)amino)methyl)-3,4-dihydronaphthalen-1(2H)-one) in framework a large X-ray crystallographic screening project against drug repurposing library, consisting 5632 approved drugs or compounds clinical phase trials. Further investigations showed that is cleaved an E1cB-like reaction...
The unique crystallization properties of the antenna protein C-phycocyanin (C-PC) from thermophilic cyanobacterium Thermosynechococcus elongatus are reported and discussed. C-PC crystallizes in hundreds significantly different conditions within a broad pH range presence wide variety precipitants additives. Remarkably, crystal dimensions vary few micrometres, as used serial crystallography, to several hundred with very diverse morphology. More than 100 single-crystal X-ray diffraction data...
Macromolecular X-ray crystallography (MX) is the most prominent method to obtain high-resolution three-dimensional knowledge of biological macromolecules. A prerequisite for that highly ordered crystalline specimen need be grown from macromolecule studied, which then prepared diffraction experiment. This preparation procedure typically involves removal crystal solution, in it was grown, soaking ligand solution or cryo-protectant and immobilizing on a mount suitable serious problem this...
Phytochelatins (PCs) are nonribosomal thiol-rich oligopeptides synthetized from glutathione (GSH) in a γ-glutamylcysteinyl transpeptidation reaction catalyzed by PC synthases (PCSs). Ubiquitous plant and present some invertebrates, PCSs involved metal detoxification homeostasis. The PCS-like enzyme the cyanobacterium Nostoc sp. (NsPCS) is considered to be an evolutionary precursor of genuine because it shows sufficient sequence similarity for homology catalytic domain eukaryotic shares...
Abstract Isovaleryl‐Coenzym A (IV‐CoA) ist eine wichtige Vorstufe für Isofettsäuren und Lipide, die in Myxobakterien essentiell Entwicklung sind. können IV‐CoA aus Acetyl‐CoA über alternative IV‐CoA‐Biosynthese (aib) herstellen. Die zentrale Reaktion aib wird durch kofaktorfreie Decarboxylase AibA/AibB katalysiert. Wir entwickelten ein effizientes Expressionssystem AibA/AibB, das Bestimmung hochaufgelöster Kristallstrukturen im Komplex mit verschiedenen Liganden ermöglichte. Durch Mutation...