9JHU

Complex structure of AtHPPD with inhibitor CLJ788

This is a non-PDB format compatible entry.

Summary for 9JHU

• Entry DOI: 10.2210/pdb9jhu/pdb
• Descriptor: 4-hydroxyphenylpyruvate dioxygenase, 2-(4-methoxyphenyl)-1,4-dimethyl-5-(2-oxidanyl-6-oxidanylidene-cyclohexen-1-yl)carbonyl-indazol-3-one, COBALT (II) ION, ... (4 entities in total)
• Functional Keywords: inhibitor, complex, oxidoreductase
• Biological source: Arabidopsis thaliana (thale cress)
• Total number of polymer chains: 1
• Total formula weight: 44807.20

Authors

Ying, R.-N.,Lin, H.-Y.,Yang, G.-F. (deposition date: 2024-09-10, release date: 2025-09-17, Last modification date: 2026-04-22)

Primary citation

Chen, L.J.,Ying, R.N.,Wang, X.Q.,Xie, D.T.,Dong, J.,Lin, H.Y.,Da-Wei, W.,Yang, G.F.
Discovery of Triketone-Indazolones as Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibiting-Based Herbicides.
J.Agric.Food Chem., 73:1112-1121, 2025

PubMed Abstract: 4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a crucial herbicide target in current research, playing an important role in the comprehensive management of resistant weeds. However, the limited crop selectivity and less effectiveness against grass weeds of many existing HPPD inhibitors, limit their further application. To address these issues, a series of novel HPPD inhibitors with fused ring structures were designed and synthesized by introducing an electron-rich indazolone ring and combining it with the classical triketone pharmacophore structure. The cocrystal structure of representative compound complexed with HPPD (HPPD) was obtained at 2.0 Å resolution to guide the optimization of the designed inhibitor. The optimization results showed that 5-(2-hydroxy-6-oxocyclohex-1-ene-1-carbonyl)-1,4-dimethyl-2-(3-(methylthio)phenyl)-1,2-dihydro-3-indazol-3-one, , was the most active HPPD inhibitor, with an IC value of 12 nM, nearly 30 times higher efficacy than mesotrione. Greenhouse herbicidal activity tests demonstrated that compound exhibited excellent herbicidal potency at 30-120 g ai/ha. Notably, it maintained high safety for peanuts even at 120 g ai/ha. Our results showed that compound is promising as a new candidate HPPD herbicide for use in the peanut fields.

PubMed: 39811931
DOI: 10.1021/acs.jafc.4c08544

Experimental method

X-RAY DIFFRACTION (1.996 Å)