Activation mechanisms of butyrylcholinesterase by 2,4,6-trinitrotoluene, 3,3-dimethylbutyl-N-n-butylcarbamate, and 2-trimethylsilyl-ethyl-N-n-butylcarbamate.
The goal of this work was to propose a possible mechanism for the butyrylcholinesterase activation by 2,4,6-trinitrotoluene (TNT), 3,3-dimethylbutyl-N-n-butylcarbamate (1), and 2-trimethylsilyl-ethyl-N-n-butylcarbamate (2). Kinetically, TNT, and compounds 1 and 2 were characterized as the nonessential activators of butyrylcholinesterase. TNT, and compounds 1 and 2 were hydrophobic compounds and were proposed to bind to the hydrophobic activator binding site, which was located outside the active site gorge of the enzyme. The conformational change from a normal active site gorge to a more accessible active site gorge of the enzyme was proposed after binding of TNT, and compounds 1 and 2 to the activator binding site of the enzyme. Therefore, TNT, and compounds 1 and 2 may act as the excess of butyrylcholine in the substrate activator for the butyrylcholinesterase catalyzed reactions.
Chiou
Shyh-Ying
SY
Division of Neurosurgery, Chung-Shan Medical University and Hospital, Taichung 402, Taiwan.
Wu
Yon-Gi
YG
Lin
Gialih
G
D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D002219:Carbamates / Q000494:pharmacology*; D020134:Catalytic Domain / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D007700:Kinetics; D015394:Molecular Structure; D011487:Protein Conformation / Q000187:drug effects; D014297:Trimethylsilyl Compounds / Q000494:pharmacology*; D014303:Trinitrotoluene / Q000494:pharmacology*
C524208:2-trimethylsilylethyl-N-n-butylcarbamate; C524207:3,3-dimethylbutyl-N-n-butylcarbamate; D002219:Carbamates; D014297:Trimethylsilyl Compounds; D014303:Trinitrotoluene; D002091:Butyrylcholinesterase