3wja
From Proteopedia
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| - | ''' | + | ==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=''> | ||
| + | == 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3WJA FirstGlance]. <br> | ||
| + | </td></tr><tr><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><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://www.rcsb.org/pdb/explore.do?structureId=3wja RCSB], [http://www.ebi.ac.uk/pdbsum/3wja PDBsum]</span></td></tr> | ||
| + | <table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:24998673</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Chan, N L.]] | ||
| + | [[Category: Chen, M C.]] | ||
| + | [[Category: Hung, H C.]] | ||
| + | [[Category: Li, S Y.]] | ||
| + | [[Category: Liu, J H.]] | ||
| + | [[Category: Yang, P C.]] | ||
| + | [[Category: Metal ion binding]] | ||
| + | [[Category: Oxidoreductase]] | ||
| + | [[Category: Oxidoreductase activity]] | ||
Revision as of 09:01, 13 August 2014
The crystal structure of human cytosolic NADP(+)-dependent malic enzyme in apo form
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