1gz4

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[[Image:1gz4.jpg|left|200px]]
 
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{{Structure
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==molecular mechanism of the regulation of human mitochondrial NAD(P)+-dependent malic enzyme by ATP and fumarate==
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|PDB= 1gz4 |SIZE=350|CAPTION= <scene name='initialview01'>1gz4</scene>, resolution 2.2&Aring;
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<StructureSection load='1gz4' size='340' side='right'caption='[[1gz4]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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|SITE= <scene name='pdbsite=AC1:Fum+Binding+Site+For+Chain+D'>AC1</scene>
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=ATP:ADENOSINE-5&#39;-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=FUM:FUMARIC+ACID'>FUM</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=TTN:TARTRONATE'>TTN</scene>
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<table><tr><td colspan='2'>[[1gz4]] 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=1GZ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1GZ4 FirstGlance]. <br>
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Malate_dehydrogenase_(oxaloacetate-decarboxylating)_(NADP(+)) Malate dehydrogenase (oxaloacetate-decarboxylating) (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.40 1.1.1.40] </span>
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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]] 2.2&#8491;</td></tr>
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|GENE=
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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=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=TTN:TARTRONATE'>TTN</scene></td></tr>
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|DOMAIN=
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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=1gz4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gz4 OCA], [https://pdbe.org/1gz4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1gz4 RCSB], [https://www.ebi.ac.uk/pdbsum/1gz4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1gz4 ProSAT]</span></td></tr>
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|RELATEDENTRY=
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1gz4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gz4 OCA], [http://www.ebi.ac.uk/pdbsum/1gz4 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1gz4 RCSB]</span>
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== Function ==
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}}
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[https://www.uniprot.org/uniprot/MAOM_HUMAN MAOM_HUMAN]
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== Evolutionary Conservation ==
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'''MOLECULAR MECHANISM OF THE REGULATION OF HUMAN MITOCHONDRIAL NAD(P)+-DEPENDENT MALIC ENZYME BY ATP AND FUMARATE'''
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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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==Overview==
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gz/1gz4_consurf.spt"</scriptWhenChecked>
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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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<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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==About this Structure==
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</jmolCheckbox>
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1GZ4 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1GZ4 OCA].
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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=1gz4 ConSurf].
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<div style="clear:both"></div>
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==Reference==
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__TOC__
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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://www.ncbi.nlm.nih.gov/pubmed/12121650 12121650]
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Malate dehydrogenase (oxaloacetate-decarboxylating) (NADP(+))]]
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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: allosteric regulation]]
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[[Category: energy metabolism]]
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[[Category: kinetic]]
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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 Sun Mar 30 20:54:21 2008''
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Current revision

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

PDB ID 1gz4

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