A chemical genetic screen uncovers a small molecule enhancer of the N-acylethanolamine degrading enzyme, fatty acid amide hydrolase, in Arabidopsis

Khan, Bibi Rafeiza; Faure, Lionel; Chapman, Kent D.; Blancaflor, Elison B.

doi:10.1038/srep41121

Title: A chemical genetic screen uncovers a small molecule enhancer of the N-acylethanolamine degrading enzyme, fatty acid amide hydrolase, in Arabidopsis

Journal Article · Mon Jan 23 00:00:00 EST 2017 · Scientific Reports

DOI:https://doi.org/10.1038/srep41121· OSTI ID:1347396

Khan, Bibi Rafeiza ^[1]; Faure, Lionel ^[2]; Chapman, Kent D. ^[3]; Blancaflor, Elison B. ^[1]

Samuel Roberts Noble Foundation Inc., Ardmore, OK (United States). Plant Biology Division
Univ. of North Texas, Denton, TX (United States). Center for Plant Lipid Research; Texas Woman's Univ., Denton, TX (United States). Biology Dept.
Univ. of North Texas, Denton, TX (United States). Center for Plant Lipid Research

N-Acylethanolamines (NAEs) are a group of fatty acid amides that play signaling roles in diverse physiological processes in eukaryotes. We used fatty acid amide hydrolase (FAAH) degrades NAE into ethanolamine and free fatty acid to terminate its signaling function. In animals, chemical inhibitors of FAAH for therapeutic treatment of pain and as tools to probe deeper into biochemical properties of FAAH. In a chemical genetic screen for small molecules that dampened the inhibitory effect of N-lauroylethanolamine (NAE 12:0) on Arabidopsis thaliana seedling growth, we identified 6-(2-methoxyphenyl)-1,3-dimethyl-5-phenyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3 H,6 H)-dione (or MDPD). MDPD alleviated the growth inhibitory effects of NAE 12:0, in part by enhancing the enzymatic activity of Arabidopsis FAAH (AtFAAH). In vitro, biochemical assays showed that MDPD enhanced the apparent Vmax of AtFAAH but did not alter the affinity of AtFAAH for its NAE substrates. Furthermore, structural analogs of MDPD did not affect AtFAAH activity or dampen the inhibitory effect of NAE 12:0 on seedling growth indicating that MDPD is a specific synthetic chemical activator of AtFAAH. Our study demonstrates the feasibility of using an unbiased chemical genetic approach to identify new pharmacological tools for manipulating FAAH- and NAE-mediated physiological processes in plants.

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Research Organization:: Univ. of North Texas, Denton, TX (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: FG02-05ER15647

OSTI ID:: 1347396

Journal Information:: Scientific Reports, Vol. 7; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 2 works

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Title: A chemical genetic screen uncovers a small molecule enhancer of the N-acylethanolamine degrading enzyme, fatty acid amide hydrolase, in Arabidopsis

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