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==Structure of the E270A Mutant Isopropylmalate dehydrogenase from Thermus thermophilus in complex with IPM, Mn and NADH==
<StructureSection load='4wuo' size='340' side='right'caption='[[4wuo]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4wuo]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Thermus_thermophilus_HB8 Thermus thermophilus HB8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WUO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WUO 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]] 2.05&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EOH:ETHANOL'>EOH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IPM:3-ISOPROPYLMALIC+ACID'>IPM</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=4wuo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wuo OCA], [https://pdbe.org/4wuo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wuo RCSB], [https://www.ebi.ac.uk/pdbsum/4wuo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wuo 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]
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== Publication Abstract from PubMed ==
The mutant E270A of Thermus thermophilus 3-isopropylmalate dehydrogenase exhibits largely reduced ( approximately 1%) catalytic activity and negligible activation by K(+) compared to the wild-type enzyme. A 3-4kcal/mol increase in the activation energy of the catalysed reaction upon this mutation could also be predicted by QM/MM calculations. In the X-ray structure of the E270A mutant a water molecule was observed to take the place of K(+). SAXS and FRET experiments revealed the essential role of E270 in stabilisation of the active domain-closed conformation of the enzyme. In addition, E270 seems to position K(+) into close proximity of the nicotinamide ring of NAD(+) and the electron-withdrawing effect of K(+) may help to polarise the aromatic ring in order to aid the hydride-transfer.

Glutamate 270 plays an essential role in K(+)-activation and domain closure of Thermus thermophilus isopropylmalate dehydrogenase.,Graczer E, Pallo A, Olah J, Szimler T, Konarev PV, Svergun DI, Merli A, Zavodszky P, Weiss MS, Vas M FEBS Lett. 2015 Jan 16;589(2):240-5. doi: 10.1016/j.febslet.2014.12.005. Epub, 2014 Dec 10. PMID:25497013<ref>PMID:25497013</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4wuo" style="background-color:#fffaf0;"></div>

==See Also==
*[[Isopropylmalate dehydrogenase|Isopropylmalate dehydrogenase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Thermus thermophilus HB8]]
[[Category: Graczer E]]
[[Category: Konarev PV]]
[[Category: Merli A]]
[[Category: Olah J]]
[[Category: Pallo A]]
[[Category: Svergun DI]]
[[Category: Szimler T]]
[[Category: Vas M]]
[[Category: Weiss MS]]
[[Category: Zavodszky P]]