Increased organophosphate scavenging in a butyrylcholinesterase mutant.
Nicotiana benthamiana plant lines expressing a reengineered human butyrylcholinesterase (BChE) with enhanced cocaine hydrolase activity were created. Subsequent purification and biochemical analysis revealed that compared to wild-type butyrylcholinesterase, the cocaine hydrolase displayed increased affinity to the organophosphate (OP) pesticides paraoxon (6.8 4x 10(-10)M vs. 1.11 x 10(-8)M) and malaoxon (9.81 x 10(-8)M vs. 5.99 x 10(-7)M). Furthermore, the cocaine hydrolase retained identical anticholinesterase binding profiles for all other compounds tested. Thus we have demonstrated a potential large-scale production platform for a multivalent antidote for cocaine and anticholinesterase poisoning.
School of Life Sciences and The Biodesign Institute, Arizona State University, Tempe, AZ 85287-4501, USA.
Brian C
BC
Geyer
Ryan R
RR
Woods
Tsafrir S
TS
Mor
D001483:Base Sequence; D002091:Butyrylcholinesterase / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D007700:Kinetics; D009154:Mutation; D010755:Organophosphates / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014026:Nicotiana
D017931:DNA Primers; D010755:Organophosphates; D011994:Recombinant Proteins; D002091:Butyrylcholinesterase