Plant-expressed cocaine hydrolase variants of butyrylcholinesterase exhibit altered allosteric effects of cholinesterase activity and increased inhibitor sensitivity

Katherine E. Larrimore, I. Can Kazan, Latha Kannan, R. Player Kendle, Tameem Jamal, Matthew Barcus, Ashini Bolia, Stephen Brimijoin, Chang Guo Zhan, Sefika Ozkan, Tsafrir Leket-Mor

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Butyrylcholinesterase (BChE) is an enzyme with broad substrate and ligand specificities and may function as a generalized bioscavenger by binding and/or hydrolyzing various xenobiotic agents and toxicants, many of which target the central and peripheral nervous systems. Variants of BChE were rationally designed to increase the enzyme's ability to hydrolyze the psychoactive enantiomer of cocaine. These variants were cloned, and then expressed using the magnICON transient expression system in plants and their enzymatic properties were investigated. In particular, we explored the effects that these site-directed mutations have over the enzyme kinetics with various substrates of BChE. We further compared the affinity of various anticholinesterases including organophosphorous nerve agents and pesticides toward these BChE variants relative to the wild type enzyme. In addition to serving as a therapy for cocaine addiction-related diseases, enhanced bioscavenging against other harmful agents could add to the practicality and versatility of the plant-derived recombinant enzyme as a multivalent therapeutic.

Original languageEnglish (US)
Article number10419
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Butyrylcholinesterase
Cholinesterases
Hydrolases
Cocaine
Enzymes
Cocaine-Related Disorders
Aptitude
Cholinesterase Inhibitors
Peripheral Nervous System
Xenobiotics
Substrate Specificity
Pesticides
Central Nervous System
Ligands
Mutation
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Plant-expressed cocaine hydrolase variants of butyrylcholinesterase exhibit altered allosteric effects of cholinesterase activity and increased inhibitor sensitivity. / Larrimore, Katherine E.; Kazan, I. Can; Kannan, Latha; Kendle, R. Player; Jamal, Tameem; Barcus, Matthew; Bolia, Ashini; Brimijoin, Stephen; Zhan, Chang Guo; Ozkan, Sefika; Leket-Mor, Tsafrir.

In: Scientific Reports, Vol. 7, No. 1, 10419, 01.12.2017.

Research output: Contribution to journalArticle

Larrimore, Katherine E. ; Kazan, I. Can ; Kannan, Latha ; Kendle, R. Player ; Jamal, Tameem ; Barcus, Matthew ; Bolia, Ashini ; Brimijoin, Stephen ; Zhan, Chang Guo ; Ozkan, Sefika ; Leket-Mor, Tsafrir. / Plant-expressed cocaine hydrolase variants of butyrylcholinesterase exhibit altered allosteric effects of cholinesterase activity and increased inhibitor sensitivity. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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