View source for 9myf


==Human malic enzyme 2 complex with inhibitor NPD-389==
<StructureSection load='9myf' size='340' side='right'caption='[[9myf]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9myf]] 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=9MYF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9MYF 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]] 2.45&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1AE5:2~3~,2~6~-dihydroxy-1~4~,3~4~-dimethoxy[1~1~,2~1~ 2~4~,3~1~-terphenyl]-2~2~,2~5~-dione'>A1AE5</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</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=9myf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9myf OCA], [https://pdbe.org/9myf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9myf RCSB], [https://www.ebi.ac.uk/pdbsum/9myf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9myf ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MAOM_HUMAN MAOM_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subtype of breast cancer with poor clinical outcomes. Malic enzyme 2 (ME2) is a mitochondrial enzyme that catalyzes the conversion of malate to pyruvate and has been proposed as a therapeutic target. ME2 is highly expressed in many cell types including TNBC cells. We sought to define the molecular and cellular consequences of ME2 inhibition to facilitate its clinical translation. Here, we systematically evaluated the cellular and molecular effects of ME2 knockdown (ME2kd) in multiple TNBC models. ME2kd had heterogeneous effects on proliferation, migration, and metabolic flexibility in TNBC cell lines. ME2kd MDA-MB-468 xenografts in nude mice grew significantly slower and conferred prolonged host survival. ME2kd caused distinct shifts in mitochondrial respiration and glycolysis, whereas metabolomic and transcriptomic analyses revealed altered tricarboxylic acid (TCA) cycle flux, glutamine consumption, and serine/glycine metabolism, partly through changes in malate-aspartate shuttle (MAS) activity. The interplay between ME2, the serine synthesis pathway and the MAS was investigated with metabolite deprivation and co-knockdown assays. Importantly, we determined the crystal structure of ME2 bound to the small-molecule inhibitor NPD-389 and identified the binding interactions that drive the inhibitory response. These findings help to clarify the role of ME2 in TNBC phenotypes and highlight the therapeutic potential of ME2 inhibition in precision oncology. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40170-025-00410-5.

Interplay between malic enzyme 2, de novo serine synthesis, and the malate-aspartate shuttle drives metabolic adaptation in triple-negative breast cancer.,Jeon JH, Slayton MD, Krinkel B, Animasahun O, Shankaran A, Wuchu F, Nenwani M, Farah Z, Burke J, Achreja A, Nilaj B, Kohagen K, Eu YH, Rosenfeld A, Collard M, Bao L, Cheng X, Kleer C, Squire C, Loomes K, Nagrath D, Merajver SD Cancer Metab. 2025 Oct 14;13(1):42. doi: 10.1186/s40170-025-00410-5. PMID:41088330<ref>PMID:41088330</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9myf" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Krinkel BA]]
[[Category: Loomes KM]]
[[Category: Squire CJ]]