Why acetylcholinesterase reactivators do not work in butyrylcholinesterase.
The pyridinium oxime therapy for treatment of organophosphate poisoning is a well established, but not sufficient method. Recent trends also focus on prophylaxis as a way of preventing even the entrance of organophosphates into the nervous system. One of the possible prophylactic methods is increasing the concentration of butyrylcholinesterase in the blood with the simultaneous administration of butyrylcholinesterase reactivators, when the enzyme is continuously reactivated by oxime. This article summarizes and sets forth the structural differences between butyrylcholinesterase and acetylcholinesterase, essential for the future design of butyrylcholinesterase reactivators. Butyrylcholinesterase lacks the reactivator aromatic binding pocket found in acetylcholinesterase, which is itself a part of the acetylcholinesterase peripheral anionic site. This difference finally renders the current acetylcholinesterase reactivators, when used in butyrylcholinesterase, non-functional.
Wiesner
Jirí
J
National Centre for Biomolecular Research, Faculty of Science, Masaryk University, Brno, Czech Republic.
Kríz
Zdenek
Z
Kuca
Kamil
K
Jun
Daniel
D
Koca
Jaroslav
J
D000110:Acetylcholinesterase / Q000737:chemistry*; D000818:Animals; D000931:Antidotes / Q000737:chemistry; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000737:chemistry*; D002801:Cholinesterase Reactivators / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D062025:Organophosphate Poisoning; D010091:Oximes / Q000737:chemistry / Q000627:therapeutic use; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D000931:Antidotes; D002801:Cholinesterase Reactivators; D010091:Oximes; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase