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| | <StructureSection load='5wj1' size='340' side='right'caption='[[5wj1]], [[Resolution|resolution]] 2.52Å' scene=''> | | <StructureSection load='5wj1' size='340' side='right'caption='[[5wj1]], [[Resolution|resolution]] 2.52Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5wj1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Arath Arath]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WJ1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WJ1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5wj1]] 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=5WJ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WJ1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=F50:ETHANEPEROXOIC+ACID'>F50</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PXD:2-(2,2-difluoroethoxy)-N-(5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)-6-(trifluoromethyl)benzenesulfonamide'>PXD</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]] 2.522Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ALS, AHAS, CSR1, TZP5, At3g48560, T8P19.70 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=3702 ARATH])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=F50:ETHANEPEROXOIC+ACID'>F50</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PXD:2-(2,2-difluoroethoxy)-N-(5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)-6-(trifluoromethyl)benzenesulfonamide'>PXD</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='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'>[https://proteopedia.org/fgij/fg.htm?mol=5wj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wj1 OCA], [https://pdbe.org/5wj1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wj1 RCSB], [https://www.ebi.ac.uk/pdbsum/5wj1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wj1 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=5wj1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wj1 OCA], [http://pdbe.org/5wj1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wj1 RCSB], [http://www.ebi.ac.uk/pdbsum/5wj1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wj1 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: Arath]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Garcia, M D]] | + | [[Category: Garcia MD]] |
| - | [[Category: Guddat, L W]] | + | [[Category: Guddat LW]] |
| - | [[Category: Lonhienne, T]] | + | [[Category: Lonhienne T]] |
| - | [[Category: Acetohydroxyacid synthase]]
| + | |
| - | [[Category: Aha]]
| + | |
| - | [[Category: Fad]]
| + | |
| - | [[Category: Herbicide]]
| + | |
| - | [[Category: Penoxsulam]]
| + | |
| - | [[Category: Thdp]]
| + | |
| - | [[Category: Thiamine aminoethenethiol diphosphate]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Triazolopyrimidine]]
| + | |
| Structural highlights
5wj1 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 2.522Å |
| 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
Acetohydroxyacid synthase (AHAS), the first enzyme in the branched amino acid biosynthesis pathway, is present only in plants and microorganisms, and it is the target of >50 commercial herbicides. Penoxsulam (PS), which is a highly effective broad-spectrum AHAS-inhibiting herbicide, is used extensively to control weed growth in rice crops. However, the molecular basis for its inhibition of AHAS is poorly understood. This is despite the availability of structural data for all other classes of AHAS-inhibiting herbicides. Here, crystallographic data for Saccharomyces cerevisiae AHAS (2.3 A) and Arabidopsis thaliana AHAS (2.5 A) in complex with PS reveal the extraordinary molecular mechanisms that underpin its inhibitory activity. The structures show that inhibition of AHAS by PS triggers expulsion of two molecules of oxygen bound in the active site, releasing them as substrates for an oxygenase side reaction of the enzyme. The structures also show that PS either stabilizes the thiamin diphosphate (ThDP)-peracetate adduct, a product of this oxygenase reaction, or traps within the active site an intact molecule of peracetate in the presence of a degraded form of ThDP: thiamine aminoethenethiol diphosphate. Kinetic analysis shows that PS inhibits AHAS by a combination of events involving FAD oxidation and chemical alteration of ThDP. With the emergence of increasing levels of resistance toward front-line herbicides and the need to optimize the use of arable land, these data suggest strategies for next generation herbicide design.
Structural insights into the mechanism of inhibition of AHAS by herbicides.,Lonhienne T, Garcia MD, Pierens G, Mobli M, Nouwens A, Guddat LW Proc Natl Acad Sci U S A. 2018 Feb 13. pii: 1714392115. doi:, 10.1073/pnas.1714392115. PMID:29440497[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
- ↑ Lonhienne T, Garcia MD, Pierens G, Mobli M, Nouwens A, Guddat LW. Structural insights into the mechanism of inhibition of AHAS by herbicides. Proc Natl Acad Sci U S A. 2018 Feb 13. pii: 1714392115. doi:, 10.1073/pnas.1714392115. PMID:29440497 doi:http://dx.doi.org/10.1073/pnas.1714392115
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