Discovering new inhibitors of bacterial glucosamine-6P synthase (GlmS) by docking simulations.
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.
Floquet
Nicolas
N
Institut de Chimie des Substances Naturelles (ICSN), UPR-2301, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
Richez
Céline
C
Durand
Philippe
P
Maigret
Bernard
B
Badet
Bernard
B
Badet-Denisot
Marie-Ange
MA
D001665:Binding Sites; D002241:Carbohydrates / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003198:Computer Simulation; D019281:Dimerization; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing) / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D008968:Molecular Conformation; D011485:Protein Binding; D012984:Software
D002241:Carbohydrates; D004791:Enzyme Inhibitors; D008024:Ligands; D005945:Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)