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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]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[3wja]] is a 2 chain structure. 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> | | <table><tr><td colspan='2'>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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Malate_dehydrogenase_(oxaloacetate-decarboxylating)_(NADP(+)) Malate dehydrogenase (oxaloacetate-decarboxylating) (NADP(+))], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.40 1.1.1.40] </span></td></tr> | | </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'>[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> | |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| 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.
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| 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<ref>PMID:24998673</ref>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 3wja" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[NADP-dependent malic enzyme|NADP-dependent malic enzyme]] | | *[[NADP-dependent malic enzyme|NADP-dependent malic enzyme]] |
| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Chan, N L]] | | [[Category: Chan N-L]] |
| [[Category: Chen, M C]] | | [[Category: Chen M-C]] |
| [[Category: Hung, H C]] | | [[Category: Hung H-C]] |
| [[Category: Li, S Y]] | | [[Category: Li S-Y]] |
| [[Category: Liu, J H]] | | [[Category: Liu J-H]] |
| [[Category: Yang, P C]] | | [[Category: Yang P-C]] |
| [[Category: Metal ion binding]]
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| [[Category: Oxidoreductase]]
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| [[Category: Oxidoreductase activity]]
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