8H6A

Crystal structure of AtHPPD complexed with YH21477

Summary for 8H6A

• Entry DOI: 10.2210/pdb8h6a/pdb
• Descriptor: 4-hydroxyphenylpyruvate dioxygenase, COBALT (II) ION, 1-[(2-chlorophenyl)methyl]-3-methyl-N-(1-methyl-1,2,3,4-tetrazol-5-yl)-2-oxidanylidene-benzimidazole-4-carboxamide, ... (4 entities in total)
• Functional Keywords: inihbitor, complex, oxidoreductase
• Biological source: Arabidopsis thaliana (thale cress)
• Total number of polymer chains: 1
• Total formula weight: 46409.48

Authors

Yang, G.-F. (deposition date: 2022-10-16, release date: 2023-10-18, Last modification date: 2025-01-01)

Primary citation

Cai, Z.M.,Huang, G.Y.,Dong, J.,Chen, L.J.,Ye, B.Q.,Lin, H.Y.,Wang, D.W.,Yang, G.F.
Discovery of Tetrazolamide-benzimidazol-2-ones as Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors.
J.Agric.Food Chem., 72:3884-3893, 2024

PubMed Abstract: 4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) is one of the most valuable herbicide targets due to its unique biological functions. In search of HPPD inhibitors with promising biological performance, we designed and synthesized a series of novel tetrazolamide-benzimidazol-2-ones using a structure-based drug design strategy. Among the synthesized compounds, 1-(2-chlorobenzyl)-3-methyl--(1-methyl-1-tetrazol-5-yl)-2-oxo-2,3-dihydro-1-benzo[]imidazole-4-carboxamide, , IC = 10 nM, was identified to be the most outstanding HPPD inhibitor, which showed more than 36-fold increased HPPD (HPPD) inhibition potency than mesotrione (IC = 363 nM). Our HPPD- complex indicated that one nitrogen atom on the tetrazole ring and the oxygen atom on the amide group formed a classical bidentate chelation interaction with the metal ion, the benzimidazol-2-one ring created a tight π-π stacking interaction with Phe381 and Phe424, and some hydrophobic interactions were also found between the -Cl-benzyl group and surrounding residues. Compound showed more than 80% inhibition against all four tested weeds at 150 g ai/ha by the postemergence application. Our results indicated that the tetrazolamide-benzimidazol-2-one scaffold may be a new lead structure for herbicide discovery.

PubMed: 38375801
DOI: 10.1021/acs.jafc.3c06798

Experimental method

X-RAY DIFFRACTION (1.601 Å)