6JX9

Structure of Y17107 complexed HPPD

6JX9 の概要

• エントリーDOI: 10.2210/pdb6jx9/pdb
• 分子名称: 4-hydroxyphenylpyruvate dioxygenase, 5-[(~{Z})-(1,3-dimethyl-5-oxidanylidene-pyrazol-4-ylidene)-oxidanyl-methyl]-2-(phenylmethyl)isoindole-1,3-dione, COBALT (II) ION, ... (4 entities in total)
• 機能のキーワード: inhibitor, complex, dioxygenase, oxidoreductase
• 由来する生物種: Arabidopsis thaliana (Mouse-ear cress)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 49308.14

構造登録者

Lin, H.Y.,Yang, G.F. (登録日: 2019-04-22, 公開日: 2020-03-11, 最終更新日: 2024-11-13)

主引用文献

He, B.,Dong, J.,Lin, H.Y.,Wang, M.Y.,Li, X.K.,Zheng, B.F.,Chen, Q.,Hao, G.F.,Yang, W.C.,Yang, G.F.
Pyrazole-Isoindoline-1,3-dione Hybrid: A Promising Scaffold for 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors.
J.Agric.Food Chem., 67:10844-10852, 2019

PubMed Abstract: The discovery of 4-hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) inhibitors has been an active area of research due to their great potential as herbicides for weed control. Starting from the binding mode of known inhibitors of HPPD, a series of HPPD inhibitors with new molecular scaffolds were designed and synthesized by hybridizing 2-benzoylethen-1-ol and isoindoline-1,3-dione fragments. The results of the in vitro tests indicated that the newly synthesized compounds showed good HPPD inhibitory activity with IC values against the recombinant HPPD (HPPD) ranging from 0.0039 μM to over 1 μM. Most promisingly, compound , 2-benzyl-5-(5-hydroxy-1,3-dimethyl-1-pyrazole-4- carbonyl)isoindoline-1,3-dione, showed the highest HPPD inhibitory activity with a value of 3.92 nM, making it approximately 10 times more potent than pyrasulfotole ( = 44 nM) and slightly more potent than mesotrione ( = 4.56 nM). In addition, the cocrystal structure of the HPPD- complex was successfully resolved at a resolution of 1.8 Å. The X-ray diffraction analysis indicated that the two carbonyl groups of 2-benzoylethen-1-ol formed a bidentate chelating interaction with the metal ion, while the isoindoline-1,3-dione moiety formed pronounced π-π stacking interactions with Phe381 and Phe424. Moreover, water-mediated hydrogen bonding interactions were observed between Asn282 and the nitrogen atoms of the pyrazole ring of . The above results showed that the pyrazole-isoindoline-1,3-dione hybrid is a promising scaffold for developing HPPD inhibitors.

PubMed: 31525997
DOI: 10.1021/acs.jafc.9b04917

実験手法

X-RAY DIFFRACTION (1.8 Å)