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New page: left|200px<br /><applet load="1tg5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tg5, resolution 1.9Å" /> '''Crystal structures of...
 
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[[Image:1tg5.jpg|left|200px]]<br /><applet load="1tg5" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1tg5, resolution 1.9&Aring;" />
'''Crystal structures of plant 4-hydroxyphenylpyruvate dioxygenases complexed with DAS645'''<br />


==Overview==
==Crystal structures of plant 4-hydroxyphenylpyruvate dioxygenases complexed with DAS645==
A high degree of selectivity toward the target site of the pest organism, is a desirable attribute for new safer agrochemicals. To assist in the, design of novel herbicides, we determined the crystal structures of the, herbicidal target enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD; EC, 1.13.11.27) from the plant Arabidopsis thaliana with and without an, herbicidal benzoylpyrazole inhibitor that potently inhibits both plant and, mammalian HPPDs. We also determined the structure of a mammalian (rat), HPPD in complex with the same nonselective inhibitor. From a screening, campaign of over 1000 HPPD inhibitors, six highly plant-selective, inhibitors were found. One of these had remarkable (&gt;1600-fold), selectivity toward the plant enzyme and was cocrystallized with, Arabidopsis HPPD. Detailed comparisons of the plant and mammalian, HPPD-ligand structures suggest a structural basis for the high degree of, plant selectivity of certain HPPD inhibitors and point to design, strategies to obtain potent and selective inhibitors of plant HPPD as, agrochemical leads.
<StructureSection load='1tg5' size='340' side='right'caption='[[1tg5]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1tg5]] 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=1TG5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TG5 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]] 1.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=645:[1-TERT-BUTYL-3-(2,4-DICHLOROPHENYL)-5-HYDROXY-1H-PYRAZOL-4-YL][2-CHLORO-4-(METHYLSULFONYL)PHENYL]METHANONE'>645</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</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=1tg5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tg5 OCA], [https://pdbe.org/1tg5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tg5 RCSB], [https://www.ebi.ac.uk/pdbsum/1tg5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tg5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HPPD_ARATH HPPD_ARATH]
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/tg/1tg5_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1tg5 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A high degree of selectivity toward the target site of the pest organism is a desirable attribute for new safer agrochemicals. To assist in the design of novel herbicides, we determined the crystal structures of the herbicidal target enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD; EC 1.13.11.27) from the plant Arabidopsis thaliana with and without an herbicidal benzoylpyrazole inhibitor that potently inhibits both plant and mammalian HPPDs. We also determined the structure of a mammalian (rat) HPPD in complex with the same nonselective inhibitor. From a screening campaign of over 1000 HPPD inhibitors, six highly plant-selective inhibitors were found. One of these had remarkable (&gt;1600-fold) selectivity toward the plant enzyme and was cocrystallized with Arabidopsis HPPD. Detailed comparisons of the plant and mammalian HPPD-ligand structures suggest a structural basis for the high degree of plant selectivity of certain HPPD inhibitors and point to design strategies to obtain potent and selective inhibitors of plant HPPD as agrochemical leads.


==About this Structure==
Structural basis for herbicidal inhibitor selectivity revealed by comparison of crystal structures of plant and mammalian 4-hydroxyphenylpyruvate dioxygenases.,Yang C, Pflugrath JW, Camper DL, Foster ML, Pernich DJ, Walsh TA Biochemistry. 2004 Aug 17;43(32):10414-23. PMID:15301540<ref>PMID:15301540</ref>
1TG5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana] with FE2 and 645 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Oxidoreductase Oxidoreductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.11.27 1.3.11.27] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1TG5 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Structural basis for herbicidal inhibitor selectivity revealed by comparison of crystal structures of plant and mammalian 4-hydroxyphenylpyruvate dioxygenases., Yang C, Pflugrath JW, Camper DL, Foster ML, Pernich DJ, Walsh TA, Biochemistry. 2004 Aug 17;43(32):10414-23. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15301540 15301540]
</div>
<div class="pdbe-citations 1tg5" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Dioxygenase 3D structures|Dioxygenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Arabidopsis thaliana]]
[[Category: Arabidopsis thaliana]]
[[Category: Oxidoreductase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Camper DL]]
[[Category: Camper, D.L.]]
[[Category: Foster ML]]
[[Category: Foster, M.L.]]
[[Category: Pernich DJ]]
[[Category: Pernich, D.J.]]
[[Category: Pflugrath JW]]
[[Category: Pflugrath, J.W.]]
[[Category: Walsh TA]]
[[Category: Walsh, T.A.]]
[[Category: Yang C]]
[[Category: Yang, C.]]
[[Category: 645]]
[[Category: FE2]]
[[Category: 4-hydroxyphenylpyruvate dioxygenase]]
[[Category: arabidopsis thaliana]]
[[Category: athppd]]
[[Category: hppd]]
 
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