title: Comparison of lipid and detergent enzyme environments for identifying inhibitors of membrane-bound energy-transducing proteins.
abstract: This study compared detergent-solubilised (soluble) and lipid-reconstituted (proteoliposome) protein to establish a high-throughput method for identifying membrane protein inhibitors. We identified inhibitors of the membrane-bound type II NADH dehydrogenase with lower lipophilicity and better potency, suggesting proteoliposome systems may be advantageous over detergent-solubilised systems for respiratory membrane proteins.
authors.affiliation: Department of Microbiology and Immunology, University of Otago, Dunedin 9054, New Zealand.
authors.forename: Elyse A
authors.initials: EA
authors.lastname: Dunn
authors.affiliation: Department of Microbiology and Immunology, University of Otago, Dunedin 9054, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1042, New Zealand. Electronic address: greg.cook@otago.ac.nz.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Cook
authors.affiliation: Department of Microbiology and Immunology, University of Otago, Dunedin 9054, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1042, New Zealand. Electronic address: adam.heikal@otago.ac.nz.
authors.forename: Adam
authors.initials: A
authors.lastname: Heikal
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D003902:Detergents / Q000737:chemistry* / Q000494:pharmacology; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D004591:Electrophoresis, Polyacrylamide Gel; D057166:High-Throughput Screening Assays / Q000379:methods; D007700:Kinetics; D008055:Lipids / Q000737:chemistry* / Q000494:pharmacology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000302:isolation & purification*; D009245:NADH Dehydrogenase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000302:isolation & purification; D011510:Proteolipids / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D003902:Detergents; D008055:Lipids; D008565:Membrane Proteins; D011510:Proteolipids; C020485:proteoliposomes; C088908:NADH dehydrogenase II; D009245:NADH Dehydrogenase
keywords: Antibiotic; Drug discovery; High throughput screening (HTS); Proteoliposomes; Type II NADH dehydrogenase (NDH-2)