A5019851198- Drug Transport and Resistance Mechanisms
- Antibiotic Resistance in Bacteria
- DNA and Nucleic Acid Chemistry
- Bacterial Genetics and Biotechnology
- Trace Elements in Health
- Cancer therapeutics and mechanisms
- Pediatric Hepatobiliary Diseases and Treatments
- Antibiotics Pharmacokinetics and Efficacy
- Electron Spin Resonance Studies
- Organic Chemistry Cycloaddition Reactions
- Insect Resistance and Genetics
- RNA and protein synthesis mechanisms
- Porphyrin and Phthalocyanine Chemistry
- Free Radicals and Antioxidants
- CRISPR and Genetic Engineering
- Enzyme Structure and Function
- Molecular Biology Techniques and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- Cardiac electrophysiology and arrhythmias
- Carcinogens and Genotoxicity Assessment
- DNA Repair Mechanisms
University of Cambridge
2016-2022
Abstract ATP-binding cassette transporters mediate the transbilayer movement of a vast number substrates in or out cells organisms ranging from bacteria to humans. Current alternating access models for ABC exporters including multidrug and Lipid A transporter MsbA Escherichia coli suggest role nucleotide as fundamental source free energy. These involve cycling between conformations with inward- outward-facing substrate-binding sites response engagement hydrolysis ATP at nucleotide-binding...
Abstract The ABC multidrug exporter MsbA mediates the translocation of lipopolysaccharides and phospholipids across plasma membrane in Gram-negative bacteria. Although is structurally well characterised, energetic requirements lipid transport remain unknown. Here, we report that, similar to small-molecule antibiotics cytotoxic agents, flopping physiologically relevant long-acyl-chain 1,2-dioleoyl (C18)-phosphatidylethanolamine proteoliposomes requires simultaneous input ATP binding...
LmrA is a bacterial ATP-binding cassette (ABC) multidrug exporter that uses metabolic energy to transport ions, cytotoxic drugs, and lipids. Voltage clamping in Port-a-Patch was used monitor electrical currents associated with the of monovalent cationic HEPES+ by single-LmrA transporters ensembles transporters. In these experiments, one proton chloride ion are effluxed together each out inner compartment, whereas two sodium ions transported into this compartment. Consequently, sodium-motive...
The expression of polyspecific membrane transporters is one important mechanism by which cells can obtain resistance to structurally different antibiotics and cytotoxic agents. These reduce intracellular drug concentrations subtoxic levels mediating efflux across the cell envelope. major facilitator superfamily multidrug transporter LmrP from Lactococcus lactis catalyses in a potential chemical proton gradient-dependent fashion. To enable interaction with protons cationic substrates,...
The bacterial heterodimeric ATP-binding cassette (ABC) multidrug exporter PatAB has a critical role in conferring antibiotic resistance multidrug-resistant infections by Streptococcus pneumoniae. As with other ABC exporters, contains two transmembrane domains that form drug translocation pathway for efflux and nucleotide-binding bind ATP, one of which is hydrolysed during transport. structural functional elements exporters determine interactions drugs couple binding to nucleotide hydrolysis...
Abstract Multidrug transporters can confer drug resistance on cells by extruding structurally unrelated compounds from the cellular interior. In transport assays, Hoechst 33342 (referred to as Hoechst) is a commonly used substrate, fluorescence of which changes in process. With three basic nitrogen atoms that be protonated, exist cationic and neutral species have different emissions abilities diffuse across cell envelopes interact with lipids intracellular nucleic acids. Due this complexity,...
Abstract Multidrug and toxic compound extrusion (MATE) transport proteins confer multidrug resistance on pathogenic microorganisms affect pharmacokinetics in mammals. Our understanding of how MATE transporters work, has mostly relied protein structures MD simulations. However, the energetics drug not been studied detail. Many utilise electrochemical H + or Na gradient to drive substrate efflux, but NorM-VC from Vibrio cholerae can both forms metabolic energy. To dissect localisation...