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2ztw
From Proteopedia
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| - | [[Image:2ztw.png|left|200px]] | ||
| - | + | ==Structure of 3-isopropylmalate dehydrogenase in complex with the inhibitor and NAD+== | |
| + | <StructureSection load='2ztw' size='340' side='right'caption='[[2ztw]], [[Resolution|resolution]] 2.79Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2ztw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus Thermus thermophilus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZTW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZTW FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.79Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DEI:(2Z)-2-HYDROXY-3-(METHYLSULFANYL)PROP-2-ENOIC+ACID'>DEI</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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=2ztw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ztw OCA], [https://pdbe.org/2ztw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ztw RCSB], [https://www.ebi.ac.uk/pdbsum/2ztw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ztw ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/LEU3_THET8 LEU3_THET8] 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.[HAMAP-Rule:MF_01033] | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zt/2ztw_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ztw ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Isopropylmalate dehydrogenase (IPMDH) is the third enzyme specific to leucine biosynthesis in microorganisms and plants, and catalyzes the oxidative decarboxylation of (2R,3S)-3-isopropylmalate to alpha-ketoisocaproate using NAD(+) as an oxidizing agent. In this study, a thia-analogue of the substrate was designed and synthesized as an inhibitor for IPMDH. The analogue showed strong competitive inhibitory activity with K(i)=62nM toward IPMDH derived from Thermus thermophilus. Moreover, the crystal structure of T. thermophilus IPMDH in a ternary complex with NAD(+) and the inhibitor has been determined at 2.8A resolution. The inhibitor exists as a decarboxylated product with an enol/enolate form in the active site. The product interacts with Arg 94, Asn 102, Ser 259, Glu 270, and a water molecule hydrogen-bonding with Arg 132. All interactions between the product and the enzyme were observed in the position associated with keto-enol tautomerization. This result implies that the tautomerization step of the thia-analogue during the IPMDH reaction is involved in the inhibition. | ||
| - | + | Crystal structure of 3-isopropylmalate dehydrogenase in complex with NAD(+) and a designed inhibitor.,Nango E, Yamamoto T, Kumasaka T, Eguchi T Bioorg Med Chem. 2009 Nov 15;17(22):7789-94. Epub 2009 Sep 19. PMID:19833522<ref>PMID:19833522</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2ztw" style="background-color:#fffaf0;"></div> | |
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==See Also== | ==See Also== | ||
*[[Isopropylmalate dehydrogenase|Isopropylmalate dehydrogenase]] | *[[Isopropylmalate dehydrogenase|Isopropylmalate dehydrogenase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| + | [[Category: Large Structures]] | ||
[[Category: Thermus thermophilus]] | [[Category: Thermus thermophilus]] | ||
| - | [[Category: Eguchi | + | [[Category: Eguchi T]] |
| - | [[Category: Kumasaka | + | [[Category: Kumasaka T]] |
| - | [[Category: Nango | + | [[Category: Nango E]] |
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Current revision
Structure of 3-isopropylmalate dehydrogenase in complex with the inhibitor and NAD+
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