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| | <StructureSection load='3r8w' size='340' side='right'caption='[[3r8w]], [[Resolution|resolution]] 2.25Å' scene=''> | | <StructureSection load='3r8w' size='340' side='right'caption='[[3r8w]], [[Resolution|resolution]] 2.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3r8w]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Arath Arath]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R8W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R8W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3r8w]] is a 4 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=3R8W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3R8W FirstGlance]. <br> |
| - | </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></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]] 2.25Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">At1g80560, IMDH, IMDH2, T21F11.11 ([https://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=ACT:ACETATE+ION'>ACT</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/3-isopropylmalate_dehydrogenase 3-isopropylmalate dehydrogenase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.85 1.1.1.85] </span></td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3r8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r8w OCA], [https://pdbe.org/3r8w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r8w RCSB], [https://www.ebi.ac.uk/pdbsum/3r8w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r8w ProSAT]</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=3r8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r8w OCA], [https://pdbe.org/3r8w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3r8w RCSB], [https://www.ebi.ac.uk/pdbsum/3r8w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3r8w ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/LEU32_ARATH LEU32_ARATH]] Catalyzes the oxidation of 3-carboxy-2-hydroxy-4-methylpentanoate (3-isopropylmalate) to 3-carboxy-4-methyl-2-oxopentanoate. The product decarboxylates to 4-methyl-2 oxopentanoate.
| + | [https://www.uniprot.org/uniprot/LEU32_ARATH LEU32_ARATH] Catalyzes the oxidation of 3-carboxy-2-hydroxy-4-methylpentanoate (3-isopropylmalate) to 3-carboxy-4-methyl-2-oxopentanoate. The product decarboxylates to 4-methyl-2 oxopentanoate. |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The methionine chain-elongation pathway is required for aliphatic glucosinolate biosynthesis in plants and evolved from leucine biosynthesis. In Arabidopsis thaliana, three 3-isopropylmalate dehydrogenases (AtIPMDHs) play key roles in methionine chain-elongation for the synthesis of aliphatic glucosinolates (e.g. AtIPMDH1) and leucine (e.g. AtIPMDH2 and AtIPMDH3). Here we elucidate the molecular basis underlying the metabolic specialization of these enzymes. The 2.25 A resolution crystal structure of AtIPMDH2 was solved to provide the first detailed molecular architecture of a plant IPMDH. Modeling of 3-isopropylmalate binding in the AtIPMDH2 active site and sequence comparisons of prokaryotic and eukaryotic IPMDH suggest that substitution of one active site residue may lead to altered substrate specificity and metabolic function. Site-directed mutagenesis of Phe-137 to a leucine in AtIPMDH1 (AtIPMDH1-F137L) reduced activity toward 3-(2'-methylthio)ethylmalate by 200-fold, but enhanced catalytic efficiency with 3-isopropylmalate to levels observed with AtIPMDH2 and AtIPMDH3. Conversely, the AtIPMDH2-L134F and AtIPMDH3-L133F mutants enhanced catalytic efficiency with 3-(2'-methylthio)ethylmalate approximately 100-fold and reduced activity for 3-isopropylmalate. Furthermore, the altered in vivo glucosinolate profile of an Arabidopsis ipmdh1 T-DNA knock-out mutant could be restored to wild-type levels by constructs expressing AtIPMDH1, AtIPMDH2-L134F, or AtIPMDH3-L133F, but not by AtIPMDH1-F137L. These results indicate that a single amino acid substitution results in functional divergence of IPMDH in planta to affect substrate specificity and contributes to the evolution of specialized glucosinolate biosynthesis from the ancestral leucine pathway.
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| - | | + | |
| - | Structural and functional evolution of isopropylmalate dehydrogenases in the leucine and glucosinolate pathways of Arabidopsis thaliana.,He Y, Galant A, Pang Q, Strul JM, Balogun SF, Jez JM, Chen S J Biol Chem. 2011 Aug 19;286(33):28794-801. Epub 2011 Jun 22. PMID:21697089<ref>PMID:21697089</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3r8w" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Isopropylmalate dehydrogenase|Isopropylmalate dehydrogenase]] | | *[[Isopropylmalate dehydrogenase|Isopropylmalate dehydrogenase]] |
| - | == References == | |
| - | <references/> | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 3-isopropylmalate dehydrogenase]] | + | [[Category: Arabidopsis thaliana]] |
| - | [[Category: Arath]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Balogun, S]] | + | [[Category: Balogun S]] |
| - | [[Category: Chen, S]] | + | [[Category: Chen S]] |
| - | [[Category: Galant, A]] | + | [[Category: Galant A]] |
| - | [[Category: He, Y]] | + | [[Category: He Y]] |
| - | [[Category: Jez, J M]] | + | [[Category: Jez JM]] |
| - | [[Category: Pang, Q]] | + | [[Category: Pang Q]] |
| - | [[Category: Strul, J M]] | + | [[Category: Strul JM]] |
| - | [[Category: 3-isopropylmalate]]
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| - | [[Category: Chloroplast]]
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| - | [[Category: Dimer]]
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| - | [[Category: Glucosinolate biosynthesis]]
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| - | [[Category: Isocitrate and isopropylmalate dehydrogenases family]]
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| - | [[Category: Leucine biosynthesis]]
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| - | [[Category: Nadh]]
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| - | [[Category: Oxidoreductase]]
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