Driving forces for ligand migration in the leucine transporter.
The potential mechanisms for driving a ligand to and through a transporter are examined for the leucine transporter using the recently published X-ray structure. Through analyses with computational methods, including investigation of electrostatic properties, site and channel identification, and docking studies, a picture emerges whereby dipolar patches which characterize the electrostatic field serve as the primary driving force to attract the ligand to the protein and begin propagation into it. The electrostatic forces are then augmented by hydrophobic forces in the transport stages, with conformational changes in the protein helping to accommodate the migration. We identify 12 sites that might be involved in ligand recognition and migration. One of these sites corresponds to the tricyclic antidepressant binding site observed in the recently published X-ray structures.
Department of Computational Chemistry and Structural Biology, H. Lundbeck A/S, 2500 Valby, Denmark.
Anne Marie
AM
Jørgensen
Sid
S
Topiol
D026905:Amino Acid Transport Systems / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D001692:Biological Transport; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D007930:Leucine / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D055672:Static Electricity; D013816:Thermodynamics
D026905:Amino Acid Transport Systems; D001426:Bacterial Proteins; D008024:Ligands; D007930:Leucine