A5046990529- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- DNA and Nucleic Acid Chemistry
- Viral gastroenteritis research and epidemiology
- Viral Infections and Immunology Research
- SARS-CoV-2 and COVID-19 Research
- RNA Research and Splicing
- Animal Virus Infections Studies
- Mass Spectrometry Techniques and Applications
- Bacteriophages and microbial interactions
- Protein Structure and Dynamics
- Advanced NMR Techniques and Applications
- Infectious Encephalopathies and Encephalitis
- Electron Spin Resonance Studies
Goethe University Frankfurt
2018-2024
Resonance Research (United States)
2023
Institute for Marine Biosciences
2020-2021
Abstract The current pandemic situation caused by the Betacoronavirus SARS-CoV-2 (SCoV2) highlights need for coordinated research to combat COVID-19. A particularly important aspect is development of medication. In addition viral proteins, structured RNA elements represent a potent alternative as drug targets. search drugs that target requires their high-resolution structural characterization. Using nuclear magnetic resonance (NMR) spectroscopy, worldwide consortium NMR researchers aims...
SARS-CoV-2 contains a positive single-stranded RNA genome of approximately 30 000 nucleotides. Within this genome, 15 elements were identified as conserved between SARS-CoV and SARS-CoV-2. By nuclear magnetic resonance (NMR) spectroscopy, we previously determined that these fold independently, in line with data from vivo ex-vivo structural probing experiments. These contain non-base-paired regions potentially harbor ligand-binding pockets. Here, performed an NMR-based screening poised...
Abstract The synthetic neomycin‐sensing riboswitch interacts with its cognate ligand neomycin as well the related antibiotics ribostamycin and paromomycin. Binding of these aminoglycosides induces a very similar ground state structure in RNA, however, only can efficiently repress translation initiation. molecular origin differences has been traced back to dynamics ligand:riboswitch complexes. Here, we combine five complementary fluorine based NMR methods accurately quantify seconds...
We present the high-resolution structure of stem-loop 4 5'-untranslated region (5_SL4) severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) genome solved by solution state nuclear magnetic resonance spectroscopy. 5_SL4 adopts an extended rod-like with a single flexible looped-out nucleotide and two mixed tandem mismatches, each composed G•U wobble base pair pyrimidine•pyrimidine mismatch, which are incorporated into structure. Both mismatches residue destabilize locally. Their...
Pseudouridine is the most frequently naturally occurring RNA modification, found in all classes of biologically functional RNAs. Compared to uridine, pseudouridine contains an additional hydrogen bond donor group and therefore widely regarded as a structure stabilizing modification. However, effects modifications on dynamics RNAs have so far only been investigated limited number different structural contexts. Here, we introduced into U-turn motif adjacent U:U closing base pair...
The neomycin sensing riboswitch is the smallest biologically functional RNA riboswitch, forming a hairpin capped with U-turn loop-a well-known motif containing conserved uracil. It was shown previously that U→C substitution of eponymous uracil does not alter structure due to C protonation at N3. Furthermore, cytosine evolutionary permitted replace in other U-turns. Here, we use molecular dynamics simulations study basis this and show structure-stabilizing monovalent cation-binding site...
Phosphorothioates (PTs) are important chemical modifications of the RNA backbone where a single nonbridging oxygen phosphate is replaced with sulfur atom. PT can stabilize RNAs by protecting them from hydrolysis and commonly used as tool to explore their function. It is, however, unclear what basic physical effects has on stability electronic structure. Here, we present molecular dynamics (MD) simulations, quantum mechanical (QM) calculations, NMR spectroscopy measurements, exploring in...
Abstract The single-stranded RNA genome of SARS-CoV-2 is highly structured. Numerous helical stem–loop structures interrupted by mismatch motifs are present in the functionally important 5′- and 3′-UTRs. These mismatches modulate local geometries feature unusual arrays hydrogen bonding donor acceptor groups. However, their conformational dynamical properties cannot be directly inferred from chemical probing difficult to predict theoretically. A motif (SL1-motif) consisting three consecutive...
Abstract The SARS-CoV-2 (SCoV-2) virus is the causative agent of ongoing COVID-19 pandemic. It contains a positive sense single-stranded RNA genome and belongs to genus Betacoronaviruses. 5′- 3′-genomic ends 30 kb SCoV-2 are potential antiviral drug targets. Major parts these sequences highly conserved among Betacoronaviruses contain cis -acting elements that affect translation replication. 31 nucleotide (nt) long stem-loop 5a (SL5a) located within 5′-untranslated region (5′-UTR) important...
Abstract The SARS-CoV-2 virus is the cause of respiratory disease COVID-19. As today, therapeutic interventions in severe COVID-19 cases are still not available as no effective therapeutics have been developed so far. Despite ongoing development a number vaccines, to fight once it has contracted will be required. Promising targets for antiviral agents against can found viral RNA genome. 5′- and 3′-genomic ends 30 kb SCoV-2 genome highly conserved among Betacoronaviruses contain structured...
Abstract SARS‐CoV‐2 contains a positive single‐stranded RNA genome of approximately 30 000 nucleotides. Within this genome, 15 elements were identified as conserved between SARS‐CoV and SARS‐CoV‐2. By nuclear magnetic resonance (NMR) spectroscopy, we previously determined that these fold independently, in line with data from vivo ex‐vivo structural probing experiments. These contain non‐base‐paired regions potentially harbor ligand‐binding pockets. Here, performed an NMR‐based screening...
Abstract The stem-loop (SL1) is the 5'-terminal structural element within single-stranded SARS-CoV-2 RNA genome. It formed by nucleotides 7–33 and consists of two short helical segments interrupted an asymmetric internal loop. This architecture conserved among Betacoronaviruses. SL1 present in genomic as well all subgenomic mRNA species produced virus during replication, thus representing a ubiquitous cis -regulatory with potential functions at stages viral life cycle. We here 1 H, 13 C 15 N...
Abstract The ongoing pandemic of the respiratory disease COVID-19 is caused by SARS-CoV-2 (SCoV2) virus. SCoV2 a member Betacoronavirus genus. 30 kb positive sense, single stranded RNA genome features 5′- and 3′-genomic ends that are highly conserved among Betacoronaviruses. These genomic contain structured cis -acting elements, which involved in regulation viral replication translation. Structural information about these potential antiviral drug targets supports development novel classes...
tRNAs are L-shaped RNA molecules of ~ 80 nucleotides that responsible for decoding the mRNA and incorporation correct amino acid into growing peptidyl-chain at ribosome. They occur in all kingdoms life both their functions, structure highly conserved. The tertiary is based on a cloverleaf-like secondary consists four base paired stems connected by three to loops. anticodon triplet, which complementary sequence mRNA, resides loop whereas attached CCA 3'-terminus molecule. exhibit very stable...
Abstract Phosphorothioates (PTs) are important chemical modifications of the RNA backbone where a single non-bridging oxygen phosphate is replaced with sulphur atom. PT can stabilize RNAs by protecting them from hydrolysis and commonly used as tool to explore their function. It is, however, unclear what basic physical effects has on stability electronic structure. Here, we present Molecular Dynamics (MD) simulations, quantum mechanical (QM) calculations, NMR spectroscopy measurements,...
Der synthetische Neomycin‐bindende Riboschalter interagiert mit seinem Liganden Neomycin sowie den verwandten Antibiotika Ribostamycin und Paromomycin. Die Bindung dieser Aminoglykoside induziert sehr ähnliche Grundzustandsstrukturen in der RNA, allerdings kann nur die Initiierung Translation effizient unterdrücken. molekulare Ursprung Unterschiede wurde auf Dynamik Ligand‐Riboschalter‐Komplexe zurückgeführt. In diesem Artikel kombinieren wir fünf komplementäre fluorbasierte NMR‐Methoden, um...