6ap6

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<StructureSection load='6ap6' size='340' side='right' caption='[[6ap6]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
<StructureSection load='6ap6' size='340' side='right' caption='[[6ap6]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6ap6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AP6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AP6 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6ap6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Pethy Pethy]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AP6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AP6 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TLF:2-[(3-CHLORO-2-METHYLPHENYL)AMINO]BENZOIC+ACID'>TLF</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=TLF:2-[(3-CHLORO-2-METHYLPHENYL)AMINO]BENZOIC+ACID'>TLF</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dnp|4dnp]]</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dnp|4dnp]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DAD2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4102 PETHY])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ap6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ap6 OCA], [http://pdbe.org/6ap6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ap6 RCSB], [http://www.ebi.ac.uk/pdbsum/6ap6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ap6 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ap6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ap6 OCA], [http://pdbe.org/6ap6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ap6 RCSB], [http://www.ebi.ac.uk/pdbsum/6ap6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ap6 ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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Strigolactones are a recently discovered class of plant hormone involved in branching, leaf senescence, root development, and plant-microbe interactions [1-6]. They are carotenoid-derived lactones, synthesized in the roots and transported acropetally to modulate axillary bud outgrowth (i.e., branching) [1, 2]. However, a receptor for strigolactones has not been identified. We have identified the DAD2 gene from petunia, an ortholog of the rice and Arabidopsis D14 genes, and present evidence for its roles in strigolactone perception and signaling. DAD2 acts in the strigolactone pathway, and the dad2 mutant is insensitive to the strigolactone analog GR24. The crystal structure of DAD2 reveals an alpha/beta hydrolase fold containing a canonical catalytic triad with a large internal cavity capable of accommodating strigolactones. In the presence of GR24 DAD2 interacts with PhMAX2A, a central component of strigolactone signaling, in a GR24 concentration-dependent manner. DAD2 can hydrolyze GR24, with mutants of the catalytic triad abolishing both this activity and the ability of DAD2 to interact with PhMAX2A. The hydrolysis products can neither stimulate the protein-protein interaction nor modulate branching. These observations suggest that DAD2 acts to bind the mobile strigolactone signal and then interacts with PhMAX2A during catalysis to initiate an SCF-mediated signal transduction pathway.
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The strigolactone (SL) family of plant hormones regulates a broad range of physiological processes affecting plant growth and development and also plays essential roles in controlling interactions with parasitic weeds and symbiotic fungi. Recent progress elucidating details of SL biosynthesis, signalling, and transport offer many opportunities for discovering new plant growth regulators via chemical interference. Here, using high throughput screening and downstream biochemical assays, we identified N-phenylanthranilic acid derivatives as potent inhibitors of the SL receptors from petunia (DAD2), rice (OsD14) and Arabidopsis (AtD14). Crystal structures of DAD2 and OsD14 in complex with inhibitors further provided detailed insights into the inhibition mechanism, and in silico modeling of 19 other plant strigolactone receptors suggested that these compounds are active across a large range of plant species. Altogether, these results provide chemical tools for investigating SL signaling and further define a framework for structure-based approaches to design and validate optimized inhibitors of SL receptors for specific plant targets.
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DAD2 Is an alpha/beta Hydrolase Likely to Be Involved in the Perception of the Plant Branching Hormone, Strigolactone.,Hamiaux C, Drummond RS, Janssen BJ, Ledger SE, Cooney JM, Newcomb RD, Snowden KC Curr Biol. 2012 Nov 6;22(21):2032-6. doi: 10.1016/j.cub.2012.08.007. Epub 2012, Sep 6. PMID:22959345<ref>PMID:22959345</ref>
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Inhibition of strigolactone receptors by N-phenylanthranilic acid derivatives: structural and functional insights.,Hamiaux C, Drummond RSM, Luo Z, Lee HW, Sharma P, Janssen BJ, Perry NB, Denny WA, Snowden KC J Biol Chem. 2018 Mar 9. pii: RA117.001154. doi: 10.1074/jbc.RA117.001154. PMID:29523686<ref>PMID:29523686</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Pethy]]
[[Category: Hamiaux, C]]
[[Category: Hamiaux, C]]
[[Category: Alpha/beta hydrolase]]
[[Category: Alpha/beta hydrolase]]
[[Category: Plant protein]]
[[Category: Plant protein]]

Revision as of 06:54, 4 April 2018

Crystal Structure of DAD2 in complex with tolfenamic acid

6ap6, resolution 1.65Å

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