Title : Molecular Modeling Evidence for His438 Flip in the Mechanism of Butyrylcholinesterase Hysteretic Behavior - Lushchekina_2014_J.Mol.Neurosci_52_44 |
Author(s) : Lushchekina SV , Nemukhin AV , Varfolomeev SD , Masson P |
Ref : Journal of Molecular Neuroscience , 52 :434 , 2014 |
Abstract :
Cholinesterases display a hysteretic behavior with certain substrates and irreversible inhibitors. For years, this behavior has remained puzzling. However, several lines of evidence indicated that it is caused by perturbation of the catalytic triad and its water environment. In the present study, using molecular dynamics simulations of Ala328Cys BCHE mutant and wild-type BCHE in the absence and presence of a co-solvent (sucrose, glycerol), we provide evidence that hysteresis originates in a flip of the catalytic triad histidine (His438). This event is controlled by water molecules that interact with active site residues. The physiological significance of this phenomenon is still an issue. |
PubMedSearch : Lushchekina_2014_J.Mol.Neurosci_52_44 |
PubMedID: 24310732 |
Lushchekina SV, Nemukhin AV, Varfolomeev SD, Masson P (2014)
Molecular Modeling Evidence for His438 Flip in the Mechanism of Butyrylcholinesterase Hysteretic Behavior
Journal of Molecular Neuroscience
52 :434
Lushchekina SV, Nemukhin AV, Varfolomeev SD, Masson P (2014)
Journal of Molecular Neuroscience
52 :434