6jx9

Structure of Y17107 complexed HPPD

spinqualitylabelsall models 6jx9, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6jx9 is a 1 chain structure with sequence from Arabidopsis thaliana. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: CO, CQC Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HPPD_ARATH Publication Abstract from PubMed 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 IC50 values against the recombinant Arabidopsis thaliana HPPD (AtHPPD) ranging from 0.0039 muM to over 1 muM. Most promisingly, compound 4ae, 2-benzyl-5-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4- carbonyl)isoindoline-1,3-dione, showed the highest AtHPPD inhibitory activity with a Ki value of 3.92 nM, making it approximately 10 times more potent than pyrasulfotole (Ki = 44 nM) and slightly more potent than mesotrione (Ki = 4.56 nM). In addition, the cocrystal structure of the AtHPPD-4ae complex was successfully resolved at a resolution of 1.8 A. 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 pi-pi 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 4ae. The above results showed that the pyrazole-isoindoline-1,3-dione hybrid is a promising scaffold for developing HPPD inhibitors. Pyrazole-Isoindoline-1,3-dione Hybrid: A Promising Scaffold for 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors.,He B, Dong J, Lin HY, Wang MY, Li XK, Zheng BF, Chen Q, Hao GF, Yang WC, Yang GF J Agric Food Chem. 2019 Oct 2;67(39):10844-10852. doi: 10.1021/acs.jafc.9b04917. , Epub 2019 Sep 24. PMID:31525997 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dioxygenase 3D structures

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