View source for 5ywk


==Crystal structure of Arabidopsis thaliana HPPD complexed with Benquitrione-Methyl==
<StructureSection load='5ywk' size='340' side='right'caption='[[5ywk]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ywk]] is a 2 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=5YWK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YWK 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]] 2.804&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=92X:1,5-dimethyl-3-(2-methylphenyl)-6-(2-oxidanyl-6-oxidanylidene-cyclohexen-1-yl)carbonyl-quinazoline-2,4-dione'>92X</scene>, <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</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=5ywk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ywk OCA], [https://pdbe.org/5ywk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ywk RCSB], [https://www.ebi.ac.uk/pdbsum/5ywk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ywk 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 recognized as one of the most promising targets in the field of herbicide innovation considering the severity of weed resistance currently. In a persistent effort to develop effective HPPD-inhibiting herbicides, a structure-guided strategy was carried out to perform the structural optimization for triketone-quinazoline-2,4-diones, a novel HPPD inhibitor scaffold first discovered in our lab. Herein, starting from the crystal structure of Arabidopsis thaliana (At)HPPD complexed with 6-(2-hydroxy-6-oxocyclohex-1-ene-1-carbonyl)-1,5-dimethyl-3-(o-tolyl)quinazoline-2,4(1H,3H)-dione (MBQ), three subseries of quinazoline-2,4-dione derivatives were designed and prepared by optimizing the hydrophobic interactions between the side chain of the core structure at the R(1) position and the hydrophobic pocket at the active site entrance of AtHPPD. 6-(2-Hydroxy-6-oxocyclohex-1-ene-1-carbonyl)-1,5-dimethyl-3-(3-(trimethylsilyl)prop-2-yn-1-yl)quinazoline-2,4(1H,3H)-dione (60) with the best inhibitory activity against AtHPPD was identified to be the first subnanomolar-range AtHPPD inhibitor (K(i) = 0.86 nM), which significantly outperformed that of the lead compound MBQ (K(i) = 8.2 nM). Further determination of the crystal structure of AtHPPD in complex with compound 60 (1.85 A) and the binding energy calculation provided a molecular basis for the understanding of its high efficiency. Additionally, the greenhouse assay indicated that 6-(2-hydroxy-6-oxocyclohex-1-ene-1-carbonyl)-1,5-dimethyl-3-propylquinazoline-2,4(1H,3H)-dione (28) and compound 60 showed acceptable crop safety against peanut and good herbicidal activity with a broad spectrum. Moreover, compound 28 also showed superior selectivity for wheat at the dosage of 120 g ai/ha and favorable herbicidal efficacy toward the gramineous weeds at the dosage of as low as 30 g ai/ha. We believe that compounds 28 and 60 have promising prospects as new herbicide candidates for wheat and peanut fields.

Structure-Guided Discovery of Silicon-Containing Subnanomolar Inhibitor of Hydroxyphenylpyruvate Dioxygenase as a Potential Herbicide.,Qu RY, Nan JX, Yan YC, Chen Q, Ndikuryayo F, Wei XF, Yang WC, Lin HY, Yang GF J Agric Food Chem. 2021 Jan 13;69(1):459-473. doi: 10.1021/acs.jafc.0c03844. Epub , 2021 Jan 4. PMID:33395281<ref>PMID:33395281</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5ywk" 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 WC]]