Simple β-lactones are potent irreversible antagonists for strigolactone receptors

Xiang, Haibo; Yao, Ruifeng; Quan, Tianfei; Wang, Fei; Chen, Li; Du, Xuewei; Zhang, Wenhao; Deng, Haiteng; Xie, Daoxin; Luo, Tuoping

doi:10.1038/cr.2017.105

Cited by 30 publications

(21 citation statements)

References 15 publications

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“…This study demonstrates the utility of molecular simulations approaches in providing mechanistic insights into fundamental questions in the field of plant biology 42,43 . Due to the importance of strigolactone signaling in crop productivity and parasitic weed germination, there is great interest in developing strigolactone signalling antagonists [44][45][46][47] . The factors we have identified that modulate ligand selectivity in strigolactone receptors can be used to inform the design of selective signalling agonists to enhance shoot branching in crops, induce suicidal germination in parasitic weeds, or prevent parasitic weed germination.…”

Section: Discussionmentioning

confidence: 99%

Role of substrate recognition in modulating strigolactone receptor selectivity in witchweed

Chen

White²,

Nelson³

et al. 2020

Preprint

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Witchweed, or Striga hermonthica, is a parasitic weed that destroys billions of dollars worth of crops globally every year. Its germination is stimulated by strigolactones exuded by its host plants. Despite high sequence, structure, and ligand binding site conservation across different plant species, one strigolactone receptor in witchweed (Sh HTL7) uniquely exhibits a picomolar EC50 for downstream signaling. Previous biochemical and structural analyses have hypothesized that this unique ligand sensitivity can be attributed to a large binding pocket volume in Sh HTL7 resulting in enhanced ability to bind substrates. Additional structural details of the substrate binding process can help explain its role in modulating the ligand selectivity. Using long-timescale molecular dynamics simulations, we demonstrate that mutations at the entrance of the binding pocket facilitate a more direct ligand binding pathway to Sh HTL7, whereas hydrophobicity at the binding pocket entrance results in a stable “anchored” state. We also demonstrate that several residues on the D-loop of At D14 stabilize catalytically inactive conformations. Finally, we show that strigolactone selectivity is not modulated by binding pocket volume. Our results indicate that while ligand binding is not the sole modulator of strigolactone receptor selectivity, it is a significant contributing factor. These results can be used to inform the design of selective antagonists for strigolactone receptors in witchweed.

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Section: Discussionmentioning

confidence: 99%

Role of substrate recognition in modulating strigolactone receptor selectivity in witchweed

Chen

White²,

Nelson³

et al. 2020

Preprint

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“…Recently, Xiang et al reported that β-lactones covalently bind to Arabidopsis D14 and inhibit the activity of AtD14 as an SL receptor ( 7 ). Here, we used 1,2,3-triazole ureas because they are easily synthesized using a simple scheme.…”

Section: Discussionmentioning

confidence: 99%

Triazole ureas covalently bind to strigolactone receptors and regulate signaling

Nakamura

Hirabayashi²,

Miyakawa

et al. 2018

Preprint

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Strigolactones (SLs), a class of plant hormones with multiple functions, mediate plant-plant and plant-microorganism communications in the rhizosphere. In this study, we developed potent strigolactone antagonists, which covalently bind to the strigolactone receptor D14, by preparing an array of triazole urea compounds. Using yeast two-hybrid assays and rice tillering assays, we identified a triazole urea compound KK094 as a potent inhibitor of strigolactone receptors. The LC-MS/MS analysis and X-ray crystallography concluded that KK094 was hydrolyzed by D14, and that a reaction product of this degradation covalently binds to the Ser residue of the catalytic triad of D14. We also identified KK052 and KK073, whose effects on D14–D53/D14–SLR1 complex formation were opposite due to a trifluoromethyl group on its benzene ring. These results demonstrate that triazole urea compounds are potentially powerful tools for agricultural application and may be useful for the elucidation of the complicated mechanism underlying SL-perception.

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“…Germain et al [382] synthesized another series of profluorescent molecular probes by coupling the butenolide D-ring to a 4-methylcoumarin (DiFMU) fluorophore (GC242, 192; Figure 9(A)), whose hydrolysis can be quantified by observing the fluorescence emitted from free DiFMU. These fluorescent reporters are expected to extend existing methodologies in SL signal studies, including evaluation of the enzyme kinetics of SL receptors and chemical affinity for receptors [381][382][383][384].…”

Section: Achievements and Prospects Of Chemical Geneticsmentioning

confidence: 99%

“…A chemical screening in Arabidopsis identified soporidine (SOP, 194; Figure 9(A)), which inhibits the activity of ShHTL7, an SL receptor in Striga [386], and suppresses Striga germination without inducing obvious phenotypical changes in rice [383]. Intriguingly, Xiang et al [384] developed multiple β-lactones, such as TFQ0011 (195, Figure 9(A)), which introduces a covalent modification of SL receptors and displays an irreversible antagonistic activity against GR24 for AtD14 and ShHTL7. This irreversible inhibition of the SL receptor by β-lactone suggests that, similar to 4BD derivatives, inhibitors with selectivity for specific targets can be developed through SAR studies of the phenyl moiety.…”

Section: Achievements and Prospects Of Chemical Geneticsmentioning

confidence: 99%

Chemical regulators of plant hormones and their applications in basic research and agriculture*

Jiang

Asami

2018

Bioscience, Biotechnology, and Biochemistry

119

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Plant hormones are small molecules that play versatile roles in regulating plant growth, development, and responses to the environment. Classic methodologies, including genetics, analytic chemistry, biochemistry, and molecular biology, have contributed to the progress in plant hormone studies. In addition, chemical regulators of plant hormone functions have been important in such studies. Today, synthetic chemicals, including plant growth regulators, are used to study and manipulate biological systems, collectively referred to as chemical biology. Here, we summarize the available chemical regulators and their contributions to plant hormone studies. We also pose questions that remain to be addressed in plant hormone studies and that might be solved with the help of chemical regulators.

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Simple β-lactones are potent irreversible antagonists for strigolactone receptors

Cited by 30 publications

References 15 publications

Role of substrate recognition in modulating strigolactone receptor selectivity in witchweed

Role of substrate recognition in modulating strigolactone receptor selectivity in witchweed

Triazole ureas covalently bind to strigolactone receptors and regulate signaling

Chemical regulators of plant hormones and their applications in basic research and agriculture*

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