5ze4: Difference between revisions
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==The structure of holo- structure of DHAD complex with [2Fe-2S] cluster== | ==The structure of holo- structure of DHAD complex with [2Fe-2S] cluster== | ||
<StructureSection load='5ze4' size='340' side='right' caption='[[5ze4]], [[Resolution|resolution]] 2.11Å' scene=''> | <StructureSection load='5ze4' size='340' side='right'caption='[[5ze4]], [[Resolution|resolution]] 2.11Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5ze4]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5ze4]] 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=5ZE4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZE4 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.11Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5ze4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ze4 OCA], [https://pdbe.org/5ze4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ze4 RCSB], [https://www.ebi.ac.uk/pdbsum/5ze4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ze4 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/ILVD_ARATH ILVD_ARATH] Catalyzes the dehydration of 2,3-dihydroxy-3-isovalerate or 2,3-dihydroxy-3-methylvalerate to the 2-oxo acids 3-methyl-2-oxobutanoate (3MOB) or 3-methyl-2-oxopentanoate (3MOP).<ref>PMID:12242394</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Arabidopsis thaliana]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Gan | [[Category: Gan J]] | ||
[[Category: Tang | [[Category: Tang Y]] | ||
[[Category: Wu | [[Category: Wu L]] | ||
[[Category: Yan | [[Category: Yan Y]] | ||
[[Category: Zang | [[Category: Zang X]] | ||
[[Category: Zhou | [[Category: Zhou J]] | ||
Latest revision as of 11:52, 22 November 2023
The structure of holo- structure of DHAD complex with [2Fe-2S] clusterThe structure of holo- structure of DHAD complex with [2Fe-2S] cluster
Structural highlights
FunctionILVD_ARATH Catalyzes the dehydration of 2,3-dihydroxy-3-isovalerate or 2,3-dihydroxy-3-methylvalerate to the 2-oxo acids 3-methyl-2-oxobutanoate (3MOB) or 3-methyl-2-oxopentanoate (3MOP).[1] Publication Abstract from PubMedBioactive natural products have evolved to inhibit specific cellular targets and have served as lead molecules for health and agricultural applications for the past century(1-3). The post-genomics era has brought a renaissance in the discovery of natural products using synthetic-biology tools(4-6). However, compared to traditional bioactivity-guided approaches, genome mining of natural products with specific and potent biological activities remains challenging(4). Here we present the discovery and validation of a potent herbicide that targets a critical metabolic enzyme that is required for plant survival. Our approach is based on the co-clustering of a self-resistance gene in the natural-product biosynthesis gene cluster(7-9), which provides insight into the potential biological activity of the encoded compound. We targeted dihydroxy-acid dehydratase in the branched-chain amino acid biosynthetic pathway in plants; the last step in this pathway is often targeted for herbicide development(10). We show that the fungal sesquiterpenoid aspterric acid, which was discovered using the method described above, is a sub-micromolar inhibitor of dihydroxy-acid dehydratase that is effective as a herbicide in spray applications. The self-resistance gene astD was validated to be insensitive to aspterric acid and was deployed as a transgene in the establishment of plants that are resistant to aspterric acid. This herbicide-resistance gene combination complements the urgent ongoing efforts to overcome weed resistance(11). Our discovery demonstrates the potential of using a resistance-gene-directed approach in the discovery of bioactive natural products. Resistance-gene-directed discovery of a natural-product herbicide with a new mode of action.,Yan Y, Liu Q, Zang X, Yuan S, Bat-Erdene U, Nguyen C, Gan J, Zhou J, Jacobsen SE, Tang Y Nature. 2018 Jul;559(7714):415-418. doi: 10.1038/s41586-018-0319-4. Epub 2018 Jul, 11. PMID:29995859[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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