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[[Image:1uxk.jpg|left|200px]]


{{Structure
==Large improvement in the thermal stability of a tetrameric malate dehydrogenase by single point mutations at the dimer-dimer interface==
|PDB= 1uxk |SIZE=350|CAPTION= <scene name='initialview01'>1uxk</scene>, resolution 1.80&Aring;
<StructureSection load='1uxk' size='340' side='right'caption='[[1uxk]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
|SITE= <scene name='pdbsite=AC1:Cd+Binding+Site+For+Chain+C'>AC1</scene>
== Structural highlights ==
|LIGAND= <scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>
<table><tr><td colspan='2'>[[1uxk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Chloroflexus_aurantiacus Chloroflexus aurantiacus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UXK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1UXK FirstGlance]. <br>
|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Malate_dehydrogenase Malate dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.37 1.1.1.37] </span>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
|GENE=
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr>
|DOMAIN=
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1uxk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uxk OCA], [https://pdbe.org/1uxk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1uxk RCSB], [https://www.ebi.ac.uk/pdbsum/1uxk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1uxk ProSAT]</span></td></tr>
|RELATEDENTRY=
</table>
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1uxk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uxk OCA], [http://www.ebi.ac.uk/pdbsum/1uxk PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1uxk RCSB]</span>
== Function ==
}}
[https://www.uniprot.org/uniprot/MDH_CHLAA MDH_CHLAA] Catalyzes the reversible oxidation of malate to oxaloacetate.[HAMAP-Rule:MF_00487]
== 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/ux/1uxk_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=1uxk ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The stability of tetrameric malate dehydrogenase from the green phototrophic bacterium Chloroflexus aurantiacus (CaMDH) is at least in part determined by electrostatic interactions at the dimer-dimer interface. Since previous studies had indicated that the thermal stability of CaMDH becomes lower with increasing pH, attempts were made to increase the stability by removal of (excess) negative charge at the dimer-dimer interface. Mutation of Glu165 to Gln or Lys yielded a dramatic increase in thermal stability at pH 7.5 (+23.6 -- + 23.9 degrees C increase in apparent t(m)) and a more moderate increase at pH 4.4 (+4.6 -- + 5.4 degrees C). The drastically increased stability at neutral pH was achieved without forfeiture of catalytic performance at low temperatures. The crystal structures of the two mutants showed only minor structural changes close to the mutated residues, and indicated that the observed stability effects are solely due to subtle changes in the complex network of electrostatic interactions in the dimer-dimer interface. Both mutations reduced the concentration dependency of thermal stability, suggesting that the oligomeric structure had been reinforced. Interestingly, the two mutations had similar effects on stability, despite the charge difference between the introduced side-chains. Together with the loss of concentration dependency, this may indicate that both E165Q and E165K stabilize CaMDH to such an extent that disruption of the inter-dimer electrostatic network around residue 165 no longer limits kinetic thermal stability.


'''LARGE IMPROVEMENT IN THE THERMAL STABILITY OF A TETRAMERIC MALATE DEHYDROGENASE BY SINGLE POINT MUTATIONS AT THE DIMER-DIMER INTERFACE'''
Large improvement in the thermal stability of a tetrameric malate dehydrogenase by single point mutations at the dimer-dimer interface.,Bjork A, Dalhus B, Mantzilas D, Sirevag R, Eijsink VG J Mol Biol. 2004 Aug 27;341(5):1215-26. PMID:15321717<ref>PMID:15321717</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1uxk" style="background-color:#fffaf0;"></div>


==Overview==
==See Also==
The stability of tetrameric malate dehydrogenase from the green phototrophic bacterium Chloroflexus aurantiacus (CaMDH) is at least in part determined by electrostatic interactions at the dimer-dimer interface. Since previous studies had indicated that the thermal stability of CaMDH becomes lower with increasing pH, attempts were made to increase the stability by removal of (excess) negative charge at the dimer-dimer interface. Mutation of Glu165 to Gln or Lys yielded a dramatic increase in thermal stability at pH 7.5 (+23.6 -- + 23.9 degrees C increase in apparent t(m)) and a more moderate increase at pH 4.4 (+4.6 -- + 5.4 degrees C). The drastically increased stability at neutral pH was achieved without forfeiture of catalytic performance at low temperatures. The crystal structures of the two mutants showed only minor structural changes close to the mutated residues, and indicated that the observed stability effects are solely due to subtle changes in the complex network of electrostatic interactions in the dimer-dimer interface. Both mutations reduced the concentration dependency of thermal stability, suggesting that the oligomeric structure had been reinforced. Interestingly, the two mutations had similar effects on stability, despite the charge difference between the introduced side-chains. Together with the loss of concentration dependency, this may indicate that both E165Q and E165K stabilize CaMDH to such an extent that disruption of the inter-dimer electrostatic network around residue 165 no longer limits kinetic thermal stability.
*[[Malate Dehydrogenase 3D structures|Malate Dehydrogenase 3D structures]]
 
== References ==
==About this Structure==
<references/>
1UXK is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Chloroflexus_aurantiacus Chloroflexus aurantiacus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UXK OCA].
__TOC__
 
</StructureSection>
==Reference==
Large improvement in the thermal stability of a tetrameric malate dehydrogenase by single point mutations at the dimer-dimer interface., Bjork A, Dalhus B, Mantzilas D, Sirevag R, Eijsink VG, J Mol Biol. 2004 Aug 27;341(5):1215-26. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15321717 15321717]
[[Category: Chloroflexus aurantiacus]]
[[Category: Chloroflexus aurantiacus]]
[[Category: Malate dehydrogenase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Bjork A]]
[[Category: Bjork, A.]]
[[Category: Dalhus B]]
[[Category: Dalhus, B.]]
[[Category: Eijsink VGH]]
[[Category: Eijsink, V G.H.]]
[[Category: Mantzilas D]]
[[Category: Mantzilas, D.]]
[[Category: Sirevag R]]
[[Category: Sirevag, R.]]
[[Category: malate dehydrogenase]]
[[Category: oxidoreductase]]
[[Category: tricarboxylic acid cycle]]
 
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