7bsk: Difference between revisions
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==Crystal structure of human ME2 R67Q mutant== | |||
<StructureSection load='7bsk' size='340' side='right'caption='[[7bsk]], [[Resolution|resolution]] 2.55Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7bsk]] 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=7BSK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BSK FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.55Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></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=7bsk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bsk OCA], [https://pdbe.org/7bsk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bsk RCSB], [https://www.ebi.ac.uk/pdbsum/7bsk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bsk ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/MAOM_HUMAN MAOM_HUMAN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Human mitochondrial NAD(P)(+)-dependent malic enzyme (ME2) is well recognized to associate with cancer cell metabolism, and the single nucleotide variants (SNVs) of ME2 may play a role in enzyme regulation. Here we reported that the SNVs of ME2 occurring in the allosteric sites lead to inactivation or overactivation of ME2. Two ME2-SNVs, ME2_R67Q and ME2-R484W, that demonstrated inactivating or overactivating enzyme activities of ME2, respectively, have different impact toward the cells. The cells with overactivating SNV enzyme, ME2_R484W, grow more rapidly and are more resistant to cellular senescence than the cells with wild-type or inactivating SNV enzyme, ME2_R67Q. Crystal structures of these two ME2-SNVs reveal that ME2_R67Q was an inactivating "dead form," and ME2_R484W was an overactivating "closed form" of the enzyme. The resolved ME2-SNV structures provide a molecular basis to explain the abnormal kinetic properties of these SNV enzymes. | |||
Single nucleotide variants lead to dysregulation of the human mitochondrial NAD(P)(+)-dependent malic enzyme.,Hsieh JY, Yang HP, Tewary SK, Cheng HC, Liu YL, Tai SC, Chen WL, Hsu CH, Huang TJ, Chou CJ, Huang YN, Peng CT, Ho MC, Liu GY, Hung HC iScience. 2021 Jan 13;24(2):102034. doi: 10.1016/j.isci.2021.102034. eCollection , 2021 Feb 19. PMID:33554057<ref>PMID:33554057</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7bsk" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Malate Dehydrogenase 3D structures|Malate Dehydrogenase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Chen WL]] | |||
[[Category: Ho MC]] | |||
[[Category: Hung HC]] | |||
[[Category: Tai SC]] | |||
Latest revision as of 18:31, 29 November 2023
Crystal structure of human ME2 R67Q mutantCrystal structure of human ME2 R67Q mutant
Structural highlights
FunctionPublication Abstract from PubMedHuman mitochondrial NAD(P)(+)-dependent malic enzyme (ME2) is well recognized to associate with cancer cell metabolism, and the single nucleotide variants (SNVs) of ME2 may play a role in enzyme regulation. Here we reported that the SNVs of ME2 occurring in the allosteric sites lead to inactivation or overactivation of ME2. Two ME2-SNVs, ME2_R67Q and ME2-R484W, that demonstrated inactivating or overactivating enzyme activities of ME2, respectively, have different impact toward the cells. The cells with overactivating SNV enzyme, ME2_R484W, grow more rapidly and are more resistant to cellular senescence than the cells with wild-type or inactivating SNV enzyme, ME2_R67Q. Crystal structures of these two ME2-SNVs reveal that ME2_R67Q was an inactivating "dead form," and ME2_R484W was an overactivating "closed form" of the enzyme. The resolved ME2-SNV structures provide a molecular basis to explain the abnormal kinetic properties of these SNV enzymes. Single nucleotide variants lead to dysregulation of the human mitochondrial NAD(P)(+)-dependent malic enzyme.,Hsieh JY, Yang HP, Tewary SK, Cheng HC, Liu YL, Tai SC, Chen WL, Hsu CH, Huang TJ, Chou CJ, Huang YN, Peng CT, Ho MC, Liu GY, Hung HC iScience. 2021 Jan 13;24(2):102034. doi: 10.1016/j.isci.2021.102034. eCollection , 2021 Feb 19. PMID:33554057[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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