Increased organophosphate scavenging in a butyrylcholinesterase mutant

Brian C. Geyer; Ryan R. Woods; Tsafrir Leket-Mor

doi:10.1016/j.cbi.2008.04.012

Increased organophosphate scavenging in a butyrylcholinesterase mutant

Brian C. Geyer, Ryan R. Woods, Tsafrir Leket-Mor

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

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 (6.84 × 10^-10 M vs. 1.11 × 10^-8 M) and malaoxon (9.81 × 10^-8 M vs. 5.99 × 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.

Original language	English (US)
Pages (from-to)	376-379
Number of pages	4
Journal	Chemico-Biological Interactions
Volume	175
Issue number	1-3
DOIs	https://doi.org/10.1016/j.cbi.2008.04.012
State	Published - Sep 25 2008

Keywords

Bioscavenger
Cocaine hydrloase
Molecular pharming
Nerve agents
Pesticides
Transgenic plants

ASJC Scopus subject areas

Toxicology

Access to Document

10.1016/j.cbi.2008.04.012

Cite this

@article{aff53c81833b496c9fff0f4ea4afd5c2,

title = "Increased organophosphate scavenging in a butyrylcholinesterase mutant",

abstract = "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 (6.84 × 10-10 M vs. 1.11 × 10-8 M) and malaoxon (9.81 × 10-8 M vs. 5.99 × 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.",

keywords = "Bioscavenger, Cocaine hydrloase, Molecular pharming, Nerve agents, Pesticides, Transgenic plants",

author = "Geyer, {Brian C.} and Woods, {Ryan R.} and Tsafrir Leket-Mor",

note = "Funding Information: This work was funded by the National Institutes of Health CounterACT Program through the National Institute of Neurological Disorders and Stroke (award #U54NS058183). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the federal government. We thank David Lenz and Douglas Cerassoli for performing the experiments with nerve agents and Stephen Brimijoin for discussions.",

year = "2008",

month = sep,

day = "25",

doi = "10.1016/j.cbi.2008.04.012",

language = "English (US)",

volume = "175",

pages = "376--379",

journal = "Chemico-Biological Interactions",

issn = "0009-2797",

publisher = "Elsevier Ireland Ltd",

number = "1-3",

}

TY - JOUR

T1 - Increased organophosphate scavenging in a butyrylcholinesterase mutant

AU - Geyer, Brian C.

AU - Woods, Ryan R.

AU - Leket-Mor, Tsafrir

N1 - Funding Information: This work was funded by the National Institutes of Health CounterACT Program through the National Institute of Neurological Disorders and Stroke (award #U54NS058183). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the federal government. We thank David Lenz and Douglas Cerassoli for performing the experiments with nerve agents and Stephen Brimijoin for discussions.

PY - 2008/9/25

Y1 - 2008/9/25

N2 - 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 (6.84 × 10-10 M vs. 1.11 × 10-8 M) and malaoxon (9.81 × 10-8 M vs. 5.99 × 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.

AB - 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 (6.84 × 10-10 M vs. 1.11 × 10-8 M) and malaoxon (9.81 × 10-8 M vs. 5.99 × 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.

KW - Bioscavenger

KW - Cocaine hydrloase

KW - Molecular pharming

KW - Nerve agents

KW - Pesticides

KW - Transgenic plants

UR - http://www.scopus.com/inward/record.url?scp=50649118321&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=50649118321&partnerID=8YFLogxK

U2 - 10.1016/j.cbi.2008.04.012

DO - 10.1016/j.cbi.2008.04.012

M3 - Article

C2 - 18514178

AN - SCOPUS:50649118321

SN - 0009-2797

VL - 175

SP - 376

EP - 379

JO - Chemico-Biological Interactions

JF - Chemico-Biological Interactions

IS - 1-3

ER -

Increased organophosphate scavenging in a butyrylcholinesterase mutant

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this