6lgt
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Complex structure of HPPD with an inhibitor Y16542== | |
| + | <StructureSection load='6lgt' size='340' side='right'caption='[[6lgt]], [[Resolution|resolution]] 1.79Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6lgt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LGT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LGT FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.794Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=ED3:3-(2-chlorophenyl)-6-(1,3-dimethyl-5-oxidanyl-pyrazol-4-yl)carbonyl-1,5-dimethyl-quinazoline-2,4-dione'>ED3</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6lgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lgt OCA], [https://pdbe.org/6lgt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lgt RCSB], [https://www.ebi.ac.uk/pdbsum/6lgt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lgt ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/HPPD_ARATH HPPD_ARATH] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) has been identified as one of the most significant targets in herbicide discovery for resistant weed control. In a continuing effort to discover potent novel HPPD inhibitors, we adopted a ring-expansion strategy to design a series of novel pyrazole-quinazoline-2,4-dione hybrids based on the previously discovered pyrazole-isoindoline-1,3-dione scaffold. One compound, 3-(2-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,5-dimethyl quinazoline-2,4(1H,3H)-dione (9bj), displayed excellent potency against AtHPPD, with an IC50 value of 84 nM, which is approximately 16-fold more potent than pyrasulfotole (IC50 = 1359 nM) and 2.7-fold more potent than mesotrione (IC50 = 226 nM). Furthermore, the co-crystal structure of the AtHPPD-9bj complex (PDB ID 6LGT) was determined at a resolution of 1.75 A. Similar to the existing HPPD inhibitors, compound 9bj formed a bidentate chelating interaction with the metal ion and a pi-pi stacking interaction with Phe381 and Phe424. In contrast, o-chlorophenyl at the N3 position of quinazoline-2,4-dione with a double conformation was surrounded by hydrophobic residues (Met335, Leu368, Leu427, Phe424, Phe392, and Phe381). Remarkably, the greenhouse assay indicated that most compounds displayed excellent herbicidal activity (complete inhibition) against at least one of the tested weeds at the application rate of 150 g of active ingredient (ai)/ha. Most promisingly, compounds 9aj and 9bi not only exhibited prominent weed control effects with a broad spectrum but also showed very good crop safety to cotton, peanuts, and corn at the dose of 150 g of ai/ha. | ||
| - | + | Discovery of Novel Pyrazole-Quinazoline-2,4-dione Hybrids as 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors.,He B, Wu FX, Yu LK, Wu L, Chen Q, Hao GF, Yang WC, Lin HY, Yang GF J Agric Food Chem. 2020 May 6;68(18):5059-5067. doi: 10.1021/acs.jafc.0c00051., Epub 2020 Apr 22. PMID:32286826<ref>PMID:32286826</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6lgt" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Dioxygenase 3D structures|Dioxygenase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Arabidopsis thaliana]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Lin HY]] | ||
| + | [[Category: Yang GF]] | ||
| + | [[Category: Yang WC]] | ||
Current revision
Complex structure of HPPD with an inhibitor Y16542
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