5ywg: Difference between revisions
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==Crystal structure of Arabidopsis thaliana HPPD complexed with Mesotrione== | |||
<StructureSection load='5ywg' size='340' side='right'caption='[[5ywg]], [[Resolution|resolution]] 2.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5ywg]] 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=5YWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YWG 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]] 2.603Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=92L:2-[(4-methylsulfonyl-2-nitro-phenyl)-oxidanyl-methylidene]cyclohexane-1,3-dione'>92L</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=5ywg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ywg OCA], [https://pdbe.org/5ywg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ywg RCSB], [https://www.ebi.ac.uk/pdbsum/5ywg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ywg ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/HPPD_ARATH HPPD_ARATH] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Slow-binding inhibitors with long residence time on the target often display superior efficacy in vivo. Rationally designing inhibitors with low off-target rates is restricted by a limited understanding of the structural basis of slow-binding inhibition kinetics in enzyme-drug interactions. 4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an important target for drug and herbicide development. Although the time-dependent behavior of HPPD inhibitors has been studied for decades, its structural basis and mechanism remain unclear. Herein, we report a detailed experimental and computational study that explores structures for illustrating the slow-binding inhibition kinetics of HPPD. We observed the conformational change of Phe428 at the C-terminal alpha-helix in the inhibitor-bound structures and further identified that the inhibition kinetics of drugs are related to steric hindrance of Phe428. These detailed structural and mechanistic insights illustrate that steric hindrance is highly associated with the time-dependent behavior of HPPD inhibitors. These findings may enable rational design of new potent HPPD-targeted drugs or herbicides with longer target residence time and improved properties. DATABASE: Structure data are available in the PDB under the accession numbers 5CTO (released), 5DHW (released), and 5YWG (released). | |||
Molecular insights into the mechanism of 4-hydroxyphenylpyruvate dioxygenase inhibition: enzyme kinetics, X-ray crystallography and computational simulations.,Lin HY, Yang JF, Wang DW, Hao GF, Dong JQ, Wang YX, Yang WC, Wu JW, Zhan CG, Yang GF FEBS J. 2019 Mar;286(5):975-990. doi: 10.1111/febs.14747. Epub 2019 Jan 25. PMID:30632699<ref>PMID:30632699</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Lin | <div class="pdbe-citations 5ywg" style="background-color:#fffaf0;"></div> | ||
[[Category: Yang | |||
==See Also== | |||
*[[Dioxygenase 3D structures|Dioxygenase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Arabidopsis thaliana]] | |||
[[Category: Large Structures]] | |||
[[Category: Lin HY]] | |||
[[Category: Yang WC]] | |||