Molecular docking studies of natural cholinesterase-inhibiting steroidal alkaloids from Sarcococca saligna.
Alkaloids isolated from Sarcococca saligna significantly inhibit acetyl- and butyrylcholinesterase enzyme, suggesting discovery of inhibitors for nervous-system disorders. Studying interactions with the active site of the AChE enzyme from Torpedo californica, we have identified hydrophobic interactions inside the aromatic gorge area as the major stabilizing factor in enzyme-inhibitor complexes of these alkaloids. Molecular Dynamics simulation of a predicted complex indicates that ligand binding does not extensively alter enzyme structure, but reduces flexibility at the gorge.
Department of Theoretical Chemistry, Institute of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innrain 52a, A-6020 Innsbruck, Austria. zaheer_qasmi@hotmail.com
Zaheer-Ul-Haq
ZU
Zaheer-Ul-Haq
Bernd
B
Wellenzohn
Klaus R
KR
Liedl
Bernd M
BM
Rode
D000110:Acetylcholinesterase / Q000737:chemistry*; D000470:Alkaloids / Q000737:chemistry*; D000818:Animals; D031234:Buxaceae / Q000737:chemistry; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D013256:Steroids / Q000737:chemistry*; D014101:Torpedo
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D008024:Ligands; D013256:Steroids; D000110:Acetylcholinesterase