Publications by authors named "Roman Zadorozhnyi"
Traditional protein structure determination by magic angle spinning (MAS) solid-state NMR spectroscopy primarily relies on interatomic distances up to 8 Å, extracted from C-, N-, and H-based dipolar-based correlation experiments. Here, we show that F fast (60 kHz) MAS NMR spectroscopy can supply additional, longer distances. Using 4F-Trp,U-C,N crystalline agglutinin (OAA), we demonstrate that judiciously designed 2D and 3D F-based dipolar correlation experiments such as (H)CF, (H)CHF, and FF can yield interatomic distances in the 8-16 Å range.
View Article and Find Full Text PDFIntegrative approaches for characterizing protein dynamics: NMR, CryoEM, and computer simulations.
Curr Opin Struct Biol
February 2024
Article Synopsis
- Proteins are dynamic molecules, with their internal movements crucial for carrying out biological functions over various timescales, from picoseconds to milliseconds.
- Observing these dynamics requires a combination of experimental techniques like NMR spectroscopy and cryo-electron microscopy, along with computational methods like molecular dynamics simulations.
- The insights gained from studying protein motions can help advance the development of new therapeutic strategies.
Article Synopsis
- HIV-1 maturation inhibitors like Bevirimat (BVM) work by blocking the cleavage of a specific peptide from the virus's protein structure, potentially serving as new treatments alongside existing antiretroviral drugs.
- The study uses advanced NMR technology to visualize the interactions between BVM, the target region of the HIV virus, and a key assembly cofactor, revealing how BVM alters the virus's maturation process.
- Findings also show that certain mutations in the virus can lead to resistance against BVM by changing how the virus structure binds, offering insights for developing improved inhibitors.
Article Synopsis
- Histidine residues are crucial in proteins for functions like metal binding, enzyme activity, and proton channel regulation, influenced by their ionization state.
- A new fast MAS NMR method at 40-62 kHz is introduced to determine the protonation and tautomeric states of His residues.
- The method employs H detection, magnetization inversion techniques, and TEDOR-based filters, demonstrated using microcrystalline HIV-1 CA-SP1 protein assemblies.
Article Synopsis
- Fluorinated drugs are increasingly popular in the pharmaceutical market, and this study focuses on using advanced F magic-angle spinning nuclear magnetic resonance (NMR) spectroscopy to analyze them.
- The technique allows for quick observation of fluorine signals with high-quality spectra obtained in just minutes, enabling efficient structural characterization of drugs like Celebrex, Cipro, and others.
- The study highlights how certain spectral features are sensitive to the type of fluorine present and the drug formulation, suggesting this method could greatly enhance the rapid analysis of fluorine-containing pharmaceuticals.
Article Synopsis
- Reverse transcription, crucial for HIV-1 replication, depends on the import of deoxynucleotide triphosphates (dNTPs) through a channel in the viral capsid.
- Molecular dynamics simulations show that cooperative binding of nucleotides in the capsid enhances the passive entry of dNTPs, while certain molecules like inositol hexakisphosphate (IP6) increase this import, and benzenehexacarboxylic acid (BHC) decreases it.
- The study utilized various microscopy techniques and virological assays to demonstrate how these interactions impact HIV-1's ability to stabilize its capsid and perform reverse transcription.