8H6A

Crystal structure of AtHPPD complexed with YH21477

8H6A の概要

• エントリーDOI: 10.2210/pdb8h6a/pdb
• 分子名称: 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)
• 機能のキーワード: inihbitor, complex, oxidoreductase
• 由来する生物種: Arabidopsis thaliana (thale cress)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 46409.48

構造登録者

Yang, G.-F. (登録日: 2022-10-16, 公開日: 2023-10-18, 最終更新日: 2025-01-01)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.601 Å)