1gz3

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[[Image:1gz3.jpg|left|200px]]<br /><applet load="1gz3" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1gz3, resolution 2.3&Aring;" />
 
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'''MOLECULAR MECHANISM FOR THE REGULATION OF HUMAN MITOCHONDRIAL NAD(P)+-DEPENDENT MALIC ENZYME BY ATP AND FUMARATE'''<br />
 
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==Overview==
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==Molecular mechanism for the regulation of human mitochondrial NAD(P)+-dependent malic enzyme by ATP and fumarate==
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The regulation of human mitochondrial NAD(P)+-dependent malic enzyme (m-NAD-ME) by ATP and fumarate may be crucial for the metabolism of glutamine for energy production in rapidly proliferating tissues and tumors. Here we report the crystal structure at 2.2 A resolution of m-NAD-ME in complex with ATP, Mn2+, tartronate, and fumarate. Our structural, kinetic, and mutagenesis studies reveal unexpectedly that ATP is an active-site inhibitor of the enzyme, despite the presence of an exo binding site. The structure also reveals the allosteric binding site for fumarate in the dimer interface. Mutations in this binding site abolished the activating effects of fumarate. Comparison to the structure in the absence of fumarate indicates a possible molecular mechanism for the allosteric function of this compound.
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<StructureSection load='1gz3' size='340' side='right'caption='[[1gz3]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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==Disease==
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<table><tr><td colspan='2'>[[1gz3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GZ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GZ3 FirstGlance]. <br>
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Known disease associated with this structure: Epilepsy, idopathic generalized, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=154270 154270]]
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=FUM:FUMARIC+ACID'>FUM</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</scene></td></tr>
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==About this Structure==
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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=1gz3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gz3 OCA], [https://pdbe.org/1gz3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gz3 RCSB], [https://www.ebi.ac.uk/pdbsum/1gz3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gz3 ProSAT]</span></td></tr>
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1GZ3 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=OXL:'>OXL</scene>, <scene name='pdbligand=MN:'>MN</scene>, <scene name='pdbligand=ATP:'>ATP</scene> and <scene name='pdbligand=FUM:'>FUM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Malate_dehydrogenase_(oxaloacetate-decarboxylating) Malate dehydrogenase (oxaloacetate-decarboxylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.38 1.1.1.38] Known structural/functional Site: <scene name='pdbsite=AC1:Fum+Binding+Site+For+Chain+D'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GZ3 OCA].
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</table>
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== Function ==
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==Reference==
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[https://www.uniprot.org/uniprot/MAOM_HUMAN MAOM_HUMAN]
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Molecular mechanism for the regulation of human mitochondrial NAD(P)+-dependent malic enzyme by ATP and fumarate., Yang Z, Lanks CW, Tong L, Structure. 2002 Jul;10(7):951-60. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12121650 12121650]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gz/1gz3_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1gz3 ConSurf].
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<div style="clear:both"></div>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Malate dehydrogenase (oxaloacetate-decarboxylating)]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Lanks CW]]
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[[Category: Lanks, C W.]]
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[[Category: Tong L]]
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[[Category: Liang, T.]]
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[[Category: Yang Z]]
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[[Category: Yang, Z.]]
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[[Category: ATP]]
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[[Category: FUM]]
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[[Category: MN]]
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[[Category: OXL]]
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[[Category: allosteric regulation]]
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[[Category: energy metabolism]]
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[[Category: kinetics]]
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[[Category: mitochondrion.]]
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[[Category: nad]]
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[[Category: oxidoreductase]]
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[[Category: protein structure]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:55:34 2008''
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Current revision

Molecular mechanism for the regulation of human mitochondrial NAD(P)+-dependent malic enzyme by ATP and fumarate

PDB ID 1gz3

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