Comparison of lipid and detergent enzyme environments for identifying inhibitors of membrane-bound energy-transducing proteins

J Microbiol Methods. 2016 Jan;120:41-3. doi: 10.1016/j.mimet.2015.11.012. Epub 2015 Nov 28.

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.

Keywords: Antibiotic; Drug discovery; High throughput screening (HTS); Proteoliposomes; Type II NADH dehydrogenase (NDH-2).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / pharmacology
  • Cell Membrane / chemistry
  • Cell Membrane / drug effects
  • Detergents / chemistry*
  • Detergents / pharmacology
  • Drug Discovery
  • Drug Evaluation, Preclinical
  • Electrophoresis, Polyacrylamide Gel
  • High-Throughput Screening Assays / methods
  • Kinetics
  • Lipids / chemistry*
  • Lipids / pharmacology
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / chemistry
  • Membrane Proteins / isolation & purification*
  • NADH Dehydrogenase / antagonists & inhibitors
  • NADH Dehydrogenase / chemistry
  • NADH Dehydrogenase / isolation & purification
  • Proteolipids / chemistry
  • Proteolipids / pharmacology

Substances

  • Anti-Infective Agents
  • Detergents
  • Lipids
  • Membrane Proteins
  • Proteolipids
  • proteoliposomes
  • NADH dehydrogenase II
  • NADH Dehydrogenase