Plant-Expressed Cocaine Hydrolase Variants of Butyrylcholinesterase Exhibit Altered Allosteric Effects of Cholinesterase Activity and Increased Inhibitor Sensitivity

Authors

Katherine E. Larrimore, Arizona State University
I. Can Kazan, Arizona State University
Latha Kannan, Arizona State University
R. Player Kendle, Arizona State University
Tameem Jamal, Arizona State University
Matthew Barcus, Arizona State University
Ashini Bolia, Arizona State University
Stephen Brimijoin, Mayo Clinic
Chang-Guo Zhan, University of KentuckyFollow
S. Banu Ozkan, Arizona State University
Tsafrir S. Mor, Arizona State University

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.

Document Type

Article

Publication Date

9-5-2017

Notes/Citation Information

Published in Scientific Reports, v. 7, article no. 10419, p. 1-14.

© The Author(s) 2017

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A correction to this article is available as an additional file listed below and online at https://doi.org/10.1038/s41598-018-35441-0.

Digital Object Identifier (DOI)

https://doi.org/10.1038/s41598-017-10571-z

Funding Information

Work was supported in part by the National Institute for Drug Abuse Grant DP1 DA031340 awarded to the Mayo Clinic and subcontracted to ASU.

Related Content

All data generated or analyzed during this study are included in this published article (and its Supplementary Information files) except for the raw computational datasets that are available from the corresponding author on reasonable request.

Supplementary information accompanies this paper at doi: 10.1038/s41598-017-10571-z

Repository Citation

Larrimore, Katherine E.; Kazan, I. Can; Kannan, Latha; Kendle, R. Player; Jamal, Tameem; Barcus, Matthew; Bolia, Ashini; Brimijoin, Stephen; Zhan, Chang-Guo; Ozkan, S. Banu; and Mor, Tsafrir S., "Plant-Expressed Cocaine Hydrolase Variants of Butyrylcholinesterase Exhibit Altered Allosteric Effects of Cholinesterase Activity and Increased Inhibitor Sensitivity" (2017). Molecular Modeling and Biopharmaceutical Center Faculty Publications. 12.
https://uknowledge.uky.edu/mmbc_facpub/12