A5023768995- Drug Transport and Resistance Mechanisms
- DNA and Nucleic Acid Chemistry
- Metal complexes synthesis and properties
- Protein purification and stability
- Monoclonal and Polyclonal Antibodies Research
- Drug Solubulity and Delivery Systems
- Adenosine and Purinergic Signaling
- Glycosylation and Glycoproteins Research
- RNA Interference and Gene Delivery
- Ion channel regulation and function
- Electron Spin Resonance Studies
- Cardiac electrophysiology and arrhythmias
- Surfactants and Colloidal Systems
- Protein Interaction Studies and Fluorescence Analysis
- X-ray Diffraction in Crystallography
- Lipid Membrane Structure and Behavior
- Neuroscience and Neuropharmacology Research
AbbVie (Germany)
2023
Ruhr University Bochum
2018-2021
Abstract ABC exporters harness the energy of ATP to pump substrates across membranes. Extracellular gate opening and closure are key steps transport cycle, but underlying mechanism is poorly understood. Here, we generated a synthetic single domain antibody (sybody) that recognizes heterodimeric exporter TM287/288 exclusively in presence ATP, which was essential solve 3.2 Å crystal structure outward-facing transporter. The sybody binds an extracellular wing strongly inhibits ATPase activity...
Hydrolysis of nucleoside triphosphate (NTP) plays a key role for the function many biomolecular systems. However, chemistry catalytic reaction in terms an atomic-level understanding structural, dynamic, and free energy changes associated with it often remains unknown. Here, we report molecular mechanism adenosine (ATP) hydrolysis ATP-binding cassette (ABC) transporter BtuCD-F. Free profiles obtained from hybrid quantum mechanical/molecular mechanical (QM/MM) dynamics (MD) simulations show...
ATP-binding cassette (ABC) transporters are ATP-driven molecular machines, in which ATP binding and hydrolysis the nucleotide-binding domains (NBDs) is chemomechanically coupled to large-scale, alternating access conformational changes transmembrane (TMDs), ultimately leading translocation of substrates across biological membranes. The precise nature structural dynamics behind large-scale transition as well coupling NBD TMD motions still unresolved. In this work, we combine all-atom (MD)...
Significance The Hv1 voltage-gated proton channels are important for various physiological functions that include the extrusion of acid from cells, oxidative bursts in phagocytes, and immune response. A lack structural information under conditions has left many unanswered questions about mechanism conduction. We employed molecular dynamics simulations to generate models open closed states channel presence applied membrane potentials, without any initial assumptions on position voltage sensor...
ATP-binding cassette (ABC) transporters chemomechanically couple ATP binding and hydrolysis to large-scale conformational changes, ultimately leading substrate translocation across biological membranes. Despite recent progress in the structure determination of substrate-bound ABC exporters, inherently dynamic mechanism transport remains unclear at atomic level. In this work, we capture heterodimeric exporter TM287/288 from hyperthermophilic bacterium Thermotoga maritima using all-atom...
A critical quality attribute for liquid formulations is the absence of visible particles. Such particles may form upon polysorbate hydrolysis resulting in release free fatty acids into solution followed by precipitation. Strategies to avoid this effect are major interest pharmaceutical industry. In context, we investigated structural organization micelles alone and addition acid myristic (MA) small-angle x-ray scattering. Two complementary approaches using a model polydisperse core-shell...
ABSTRACT ABC exporters harness the energy of ATP to pump substrates across membranes. Extracellular gate opening and closure are key steps transport cycle, but underlying mechanism is poorly understood. Here, we generated a synthetic single domain antibody (sybody) that recognizes heterodimeric exporter TM287/288 exclusively in presence ATP, which was essential solve 3.2 Å crystal structure outward-facing transporter. The sybody binds an extracellular wing strongly inhibits ATPase activity...