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| | ==Crystal structure of Arabidopsis thaliana acetohydroxyacid synthase in complex with a pyrimidinyl-benzoate herbicide, bispyribac-sodium== | | ==Crystal structure of Arabidopsis thaliana acetohydroxyacid synthase in complex with a pyrimidinyl-benzoate herbicide, bispyribac-sodium== |
| - | <StructureSection load='5k3s' size='340' side='right' caption='[[5k3s]], [[Resolution|resolution]] 2.87Å' scene=''> | + | <StructureSection load='5k3s' size='340' side='right'caption='[[5k3s]], [[Resolution|resolution]] 2.87Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5k3s]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K3S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K3S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5k3s]] 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=5K3S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K3S FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6QL:2,6-BIS[(4,6-DIMETHOXYPYRIMIDIN-2-YL)OXY]BENZOIC+ACID'>6QL</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TP9:(3Z)-4-{[(4-AMINO-2-METHYLPYRIMIDIN-5-YL)METHYL]AMINO}-3-MERCAPTOPENT-3-EN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>TP9</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.873Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6QL:2,6-BIS[(4,6-DIMETHOXYPYRIMIDIN-2-YL)OXY]BENZOIC+ACID'>6QL</scene>, <scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TP9:(3Z)-4-{[(4-AMINO-2-METHYLPYRIMIDIN-5-YL)METHYL]AMINO}-3-MERCAPTOPENT-3-EN-1-YL+TRIHYDROGEN+DIPHOSPHATE'>TP9</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5k2o|5k2o]]</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=5k3s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k3s OCA], [https://pdbe.org/5k3s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k3s RCSB], [https://www.ebi.ac.uk/pdbsum/5k3s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k3s ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Acetolactate_synthase Acetolactate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.2.1.6 2.2.1.6] </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=5k3s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k3s OCA], [http://pdbe.org/5k3s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k3s RCSB], [http://www.ebi.ac.uk/pdbsum/5k3s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k3s ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ILVB_ARATH ILVB_ARATH]] Catalyzes the formation of acetolactate from pyruvate, the first step in valine and isoleucine biosynthesis.<ref>PMID:16665813</ref> <ref>PMID:2336405</ref> [:]<ref>PMID:16667374</ref> <ref>PMID:16668488</ref> <ref>PMID:8913312</ref> <ref>PMID:9355748</ref> <ref>PMID:9677339</ref> <ref>PMID:10386618</ref> | + | [https://www.uniprot.org/uniprot/ILVB_ARATH ILVB_ARATH] Catalyzes the formation of acetolactate from pyruvate, the first step in valine and isoleucine biosynthesis.<ref>PMID:16665813</ref> <ref>PMID:2336405</ref> [:]<ref>PMID:16667374</ref> <ref>PMID:16668488</ref> <ref>PMID:8913312</ref> <ref>PMID:9355748</ref> <ref>PMID:9677339</ref> <ref>PMID:10386618</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: Acetolactate synthase]] | + | [[Category: Arabidopsis thaliana]] |
| - | [[Category: Garcia, M D]] | + | [[Category: Large Structures]] |
| - | [[Category: Guddat, L W]] | + | [[Category: Garcia MD]] |
| - | [[Category: Lonhienne, T]] | + | [[Category: Guddat LW]] |
| - | [[Category: Acetohydroxyacid synthase]] | + | [[Category: Lonhienne T]] |
| - | [[Category: Aha]]
| + | |
| - | [[Category: Bispyribac-sodium]]
| + | |
| - | [[Category: Fad]]
| + | |
| - | [[Category: Herbicide]]
| + | |
| - | [[Category: Pyrimidinyl-benzoate]]
| + | |
| - | [[Category: Thiamin diphosphate]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
5k3s is a 1 chain structure with sequence from Arabidopsis thaliana. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.873Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
ILVB_ARATH Catalyzes the formation of acetolactate from pyruvate, the first step in valine and isoleucine biosynthesis.[1] [2] [:][3] [4] [5] [6] [7] [8]
Publication Abstract from PubMed
Five commercial herbicide families inhibit acetohydroxyacid synthase (AHAS, E.C. 2.2.1.6), which is the first enzyme in the branched-chain amino acid biosynthesis pathway. The popularity of these herbicides is due to their low application rates, high crop vs. weed selectivity, and low toxicity in animals. Here, we have determined the crystal structures of Arabidopsis thaliana AHAS in complex with two members of the pyrimidinyl-benzoate (PYB) and two members of the sulfonylamino-carbonyl-triazolinone (SCT) herbicide families, revealing the structural basis for their inhibitory activity. Bispyribac, a member of the PYBs, possesses three aromatic rings and these adopt a twisted "S"-shaped conformation when bound to A. thaliana AHAS (AtAHAS) with the pyrimidinyl group inserted deepest into the herbicide binding site. The SCTs bind such that the triazolinone ring is inserted deepest into the herbicide binding site. Both compound classes fill the channel that leads to the active site, thus preventing substrate binding. The crystal structures and mass spectrometry also show that when these herbicides bind, thiamine diphosphate (ThDP) is modified. When the PYBs bind, the thiazolium ring is cleaved, but when the SCTs bind, ThDP is modified to thiamine 2-thiazolone diphosphate. Kinetic studies show that these compounds not only trigger reversible accumulative inhibition of AHAS, but also can induce inhibition linked with ThDP degradation. Here, we describe the features that contribute to the extraordinarily powerful herbicidal activity exhibited by four classes of AHAS inhibitors.
Comprehensive understanding of acetohydroxyacid synthase inhibition by different herbicide families.,Garcia MD, Nouwens A, Lonhienne TG, Guddat LW Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):E1091-E1100. doi:, 10.1073/pnas.1616142114. Epub 2017 Jan 30. PMID:28137884[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mazur BJ, Chui CF, Smith JK. Isolation and characterization of plant genes coding for acetolactate synthase, the target enzyme for two classes of herbicides. Plant Physiol. 1987 Dec;85(4):1110-7. PMID:16665813
- ↑ Sathasivan K, Haughn GW, Murai N. Nucleotide sequence of a mutant acetolactate synthase gene from an imidazolinone-resistant Arabidopsis thaliana var. Columbia. Nucleic Acids Res. 1990 Apr 25;18(8):2188. PMID:2336405
- ↑ Haughn GW, Somerville CR. A Mutation Causing Imidazolinone Resistance Maps to the Csr1 Locus of Arabidopsis thaliana. Plant Physiol. 1990 Apr;92(4):1081-5. PMID:16667374
- ↑ Sathasivan K, Haughn GW, Murai N. Molecular Basis of Imidazolinone Herbicide Resistance in Arabidopsis thaliana var Columbia. Plant Physiol. 1991 Nov;97(3):1044-50. PMID:16668488
- ↑ Ott KH, Kwagh JG, Stockton GW, Sidorov V, Kakefuda G. Rational molecular design and genetic engineering of herbicide resistant crops by structure modeling and site-directed mutagenesis of acetohydroxyacid synthase. J Mol Biol. 1996 Oct 25;263(2):359-68. PMID:8913312 doi:http://dx.doi.org/10.1006/jmbi.1996.0580
- ↑ Chang AK, Duggleby RG. Expression, purification and characterization of Arabidopsis thaliana acetohydroxyacid synthase. Biochem J. 1997 Oct 1;327 ( Pt 1):161-9. PMID:9355748
- ↑ Chang AK, Duggleby RG. Herbicide-resistant forms of Arabidopsis thaliana acetohydroxyacid synthase: characterization of the catalytic properties and sensitivity to inhibitors of four defined mutants. Biochem J. 1998 Aug 1;333 ( Pt 3):765-77. PMID:9677339
- ↑ Lee YT, Chang AK, Duggleby RG. Effect of mutagenesis at serine 653 of Arabidopsis thaliana acetohydroxyacid synthase on the sensitivity to imidazolinone and sulfonylurea herbicides. FEBS Lett. 1999 Jun 11;452(3):341-5. PMID:10386618
- ↑ Garcia MD, Nouwens A, Lonhienne TG, Guddat LW. Comprehensive understanding of acetohydroxyacid synthase inhibition by different herbicide families. Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):E1091-E1100. doi:, 10.1073/pnas.1616142114. Epub 2017 Jan 30. PMID:28137884 doi:http://dx.doi.org/10.1073/pnas.1616142114
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