Molecular interaction of human brain acetylcholinesterase with a natural inhibitor huperzine-B: an enzoinformatics approach.
The present study emphasizes the molecular interactions between human brain acetylcholinesterase (AChE) and the natural ligand Huperzine-B and its comparison to 'AChE-Tolserine interactions'. Docking between Huperzine-B and AChE was performed using 'Autodock4.2'. Hydrophobic interactions and hydrogen bonds both play an equally important role in the correct positioning of Huperzine-B within the 'catalytic site' of AChE to permit docking. However, docking of Tolserine to AChE is largely dominated by hydrophobic interactions. Such information may aid in the design of versatile AChE-inhibitors, and is expected to aid in safe clinical use of Huperzine-B. Scope still remains in the determination of the three-dimensional structure of AChE-Huperzine-B complex by X-ray crystallography to validate the described data. Furthermore, this study confirms that Huperzine-B is a more efficient inhibitor of human brain AChE compared to tolserine with reference to Ki and ΔG values.
Aftab
A
Alam
Sibhghatulla
S
Shaikh
Syed S
SS
Ahmad
Mohammad A
MA
Ansari
Shahnawaz
S
Shakil
Syed M D
SM
Rizvi
Shazi
S
Shakil
Mohammad
M
Imran
Mohammad
M
Haneef
Adel M
AM
Abuzenadah
Department of Bio-Engineering, Integral University, Lucknow-226026, India. shazibiotech@gmail.com.
Mohammad A
MA
Kamal
D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology*; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D030562:Databases, Protein / Q000706:statistics & numerical data*; D006801:Humans; D008958:Models, Molecular
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; C053016:huperzine B; D000110:Acetylcholinesterase