Chemical Genetic Screening Identifies Nalacin As an Inhibitor of GH3 Amido Synthetase for Auxin Conjugation

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2022 Dec 1

PMID 36454752

Authors

Yinpeng Xie

Ying Zhu

Na Wang

Min Luo

Tsuyoshi Ota

Ruipan Guo

Ikuo Takahashi

Zongjun Yu

Yalikunjiang Aizezi

Linlin Zhang

Yan Yan

Yujie Zhang

Hongyu Bao

Yichuan Wang

Ziqiang Zhu

Ancheng C Huang

Yunde Zhao

Tadao Asami

Hongda Huang

Hongwei Guo

Kai Jiang

Affiliations

Soon will be listed here.

Abstract

Auxin inactivation is critical for plant growth and development. To develop plant growth regulators functioning in auxin inactivation pathway, we performed a phenotype-based chemical screen in Arabidopsis and identified a chemical, nalacin, that partially mimicked the effects of auxin. Genetic, pharmacological, and biochemical approaches demonstrated that nalacin exerts its auxin-like activities by inhibiting indole-3-acetic acid (IAA) conjugation that is mediated by Gretchen Hagen 3 (GH3) acyl acid amido synthetases. The crystal structure of Arabidopsis GH3.6 in complex with D4 (a derivative of nalacin) together with docking simulation analysis revealed the molecular basis of the inhibition of group II GH3 by nalacin. Sequence alignment analysis indicated broad bioactivities of nalacin and D4 as inhibitors of GH3s in vascular plants, which were confirmed, at least, in tomato and rice. In summary, our work identifies nalacin as a potent inhibitor of IAA conjugation mediated by group II GH3 that plays versatile roles in hormone-regulated plant development and has potential applications in both basic research and agriculture.

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