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| | ==The crystal structure of human cytosolic NADP(+)-dependent malic enzyme in apo form== | | ==The crystal structure of human cytosolic NADP(+)-dependent malic enzyme in apo form== |
| - | <StructureSection load='3wja' size='340' side='right' caption='[[3wja]], [[Resolution|resolution]] 2.55Å' scene=''> | + | <StructureSection load='3wja' size='340' side='right'caption='[[3wja]], [[Resolution|resolution]] 2.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3wja]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3WJA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WJA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3wja]] is a 2 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=3WJA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WJA FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ME1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.548Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></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=3wja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wja OCA], [https://pdbe.org/3wja PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wja RCSB], [https://www.ebi.ac.uk/pdbsum/3wja PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wja ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3wja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wja OCA], [http://pdbe.org/3wja PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3wja RCSB], [http://www.ebi.ac.uk/pdbsum/3wja PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3wja ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/MAOX_HUMAN MAOX_HUMAN] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Chan, N L]] | + | [[Category: Large Structures]] |
| - | [[Category: Chen, M C]] | + | [[Category: Chan N-L]] |
| - | [[Category: Hung, H C]] | + | [[Category: Chen M-C]] |
| - | [[Category: Li, S Y]] | + | [[Category: Hung H-C]] |
| - | [[Category: Liu, J H]] | + | [[Category: Li S-Y]] |
| - | [[Category: Yang, P C]] | + | [[Category: Liu J-H]] |
| - | [[Category: Metal ion binding]]
| + | [[Category: Yang P-C]] |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Oxidoreductase activity]]
| + | |
| Structural highlights
Function
MAOX_HUMAN
Publication Abstract from PubMed
Human cytosolic NADP+-dependent malic enzyme (c-NADP-ME) is neither a cooperative nor an allosteric enzyme, whereas mitochondrial NAD(P)+-dependent malic enzyme (m-NAD(P)-ME) is allosterically activated by fumarate. This study examines the molecular basis for the different allosteric properties and quaternary structural stability of m-NAD(P)-ME and c-NADP-ME. Multiple residues corresponding to the fumarate-binding site were mutated in human c-NADP-ME to correspond to those found in human m-NAD(P)-ME. Additionally, the crystal structure of the apo (ligand-free) human c-NADP-ME conformation was determined. Kinetic studies indicated no significant difference between the wild-type and mutant enzymes in Km,NADP, Km,malate, and kcat. A chimeric enzyme, [51-105]_c-NADP-ME, was designed to include the putative fumarate-binding site of m-NAD(P)-ME at the dimer interface of c-NADP-ME; however, this chimera remained nonallosteric. In addition to fumarate activation, the quaternary structural stability of c-NADP-ME and m-NAD(P)-ME is quite different; c-NADP-ME is a stable tetramer, whereas m-NAD(P)-ME exists in equilibrium between a dimer and a tetramer. The quaternary structures for the S57K/N59E/E73K/S102D and S57K/N59E/E73K/S102D/H74K/D78P/D80E/D87G mutants of c-NADP-ME are tetrameric, whereas the K57S/E59N/K73E/D102S m-NAD(P)-ME quadruple mutant is primarily monomeric with some dimer formation. These results strongly suggest that the structural features near the fumarate-binding site and the dimer interface are highly related to the quaternary structural stability of c-NADP-ME and m-NAD(P)-ME. In this study, we attempt to delineate the structural features governing the fumarate-induced allosteric activation of malic enzyme.
Structural characteristics of the nonallosteric human cytosolic malic enzyme.,Hsieh JY, Li SY, Chen MC, Yang PC, Chen HY, Chan NL, Liu JH, Hung HC Biochim Biophys Acta. 2014 Jul 3;1844(10):1773-1783. doi:, 10.1016/j.bbapap.2014.06.019. PMID:24998673[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hsieh JY, Li SY, Chen MC, Yang PC, Chen HY, Chan NL, Liu JH, Hung HC. Structural characteristics of the nonallosteric human cytosolic malic enzyme. Biochim Biophys Acta. 2014 Jul 3;1844(10):1773-1783. doi:, 10.1016/j.bbapap.2014.06.019. PMID:24998673 doi:http://dx.doi.org/10.1016/j.bbapap.2014.06.019
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