Discovering new inhibitors of bacterial glucosamine-6P synthase (GlmS) by docking simulations

Bioorg Med Chem Lett. 2007 Apr 1;17(7):1966-70. doi: 10.1016/j.bmcl.2007.01.052. Epub 2007 Jan 25.

Abstract

Results of an in silico screening of a freely accessible database encompassing 50,000 commercial compounds on bacterial glucosamine-6P synthase (Glms) are described. Each product was docked with the GOLD software in a region of 20A surrounding the sugar binding site and ranked according to its score. Among the 14 best-scored molecules, three molecules exhibited good experimental inhibition properties (IC(50)=70 microM) giving a high hit rate (H.R.: 0.23). Interestingly, these molecules are predicted to interact with a protein region that forms a pocket at the interface between the two enzyme monomers, opening the route to dimerization inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Carbohydrates / chemistry
  • Chemistry, Pharmaceutical / methods*
  • Computer Simulation
  • Dimerization
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / chemistry*
  • Inhibitory Concentration 50
  • Kinetics
  • Ligands
  • Models, Chemical
  • Molecular Conformation
  • Protein Binding
  • Software

Substances

  • Carbohydrates
  • Enzyme Inhibitors
  • Ligands
  • Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)