6JX9
Structure of Y17107 complexed HPPD
Summary for 6JX9
| Entry DOI | 10.2210/pdb6jx9/pdb |
| Descriptor | 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) |
| Functional Keywords | inhibitor, complex, dioxygenase, oxidoreductase |
| Biological source | Arabidopsis thaliana (Mouse-ear cress) |
| Total number of polymer chains | 1 |
| Total formula weight | 49308.14 |
| Authors | Lin, H.Y.,Yang, G.F. (deposition date: 2019-04-22, release date: 2020-03-11, Last modification date: 2024-11-13) |
| Primary citation | 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 Cited by 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: 31525997DOI: 10.1021/acs.jafc.9b04917 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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