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| | ==Crystal Structure Analysis of 6-phosphogluconate dehydrogenase apo-form== | | ==Crystal Structure Analysis of 6-phosphogluconate dehydrogenase apo-form== |
| - | <StructureSection load='4gwg' size='340' side='right' caption='[[4gwg]], [[Resolution|resolution]] 1.39Å' scene=''> | + | <StructureSection load='4gwg' size='340' side='right'caption='[[4gwg]], [[Resolution|resolution]] 1.39Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4gwg]] is a 1 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=4GWG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GWG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gwg]] is a 1 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=4GWG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GWG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></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]] 1.3907Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2jkv|2jkv]], [[4gwk|4gwk]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PGD, PGDH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4gwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gwg OCA], [https://pdbe.org/4gwg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gwg RCSB], [https://www.ebi.ac.uk/pdbsum/4gwg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gwg ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphogluconate_dehydrogenase_(NADP(+)-dependent,_decarboxylating) Phosphogluconate dehydrogenase (NADP(+)-dependent, decarboxylating)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.44 1.1.1.44] </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=4gwg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gwg OCA], [http://pdbe.org/4gwg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gwg RCSB], [http://www.ebi.ac.uk/pdbsum/4gwg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gwg ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/6PGD_HUMAN 6PGD_HUMAN]] Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH. | + | [https://www.uniprot.org/uniprot/6PGD_HUMAN 6PGD_HUMAN] Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH. |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | It is unclear how cancer cells coordinate glycolysis and biosynthesis to support rapidly growing tumors. We found that the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1), commonly upregulated in human cancers due to loss of TP53, contributes to biosynthesis regulation in part by controlling intracellular levels of its substrate, 3-phosphoglycerate (3-PG), and product, 2-phosphoglycerate (2-PG). 3-PG binds to and inhibits 6-phosphogluconate dehydrogenase in the oxidative pentose phosphate pathway (PPP), while 2-PG activates 3-phosphoglycerate dehydrogenase to provide feedback control of 3-PG levels. Inhibition of PGAM1 by shRNA or a small molecule inhibitor PGMI-004A results in increased 3-PG and decreased 2-PG levels in cancer cells, leading to significantly decreased glycolysis, PPP flux and biosynthesis, as well as attenuated cell proliferation and tumor growth.
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| | | | |
| - | Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth.,Hitosugi T, Zhou L, Elf S, Fan J, Kang HB, Seo JH, Shan C, Dai Q, Zhang L, Xie J, Gu TL, Jin P, Aleckovic M, Leroy G, Kang Y, Sudderth JA, Deberardinis RJ, Luan CH, Chen GZ, Muller S, Shin DM, Owonikoko TK, Lonial S, Arellano ML, Khoury HJ, Khuri FR, Lee BH, Ye K, Boggon TJ, Kang S, He C, Chen J Cancer Cell. 2012 Nov 13;22(5):585-600. doi: 10.1016/j.ccr.2012.09.020. PMID:23153533<ref>PMID:23153533</ref>
| + | ==See Also== |
| - | | + | *[[6-phosphogluconate dehydrogenase 3D structures|6-phosphogluconate dehydrogenase 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4gwg" style="background-color:#fffaf0;"></div>
| + | |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: He, C]] | + | [[Category: Large Structures]] |
| - | [[Category: Zhang, L]] | + | [[Category: He C]] |
| - | [[Category: Zhou, L]] | + | [[Category: Zhang L]] |
| - | [[Category: 6-phosphoglyconate dehydrogenase]] | + | [[Category: Zhou L]] |
| - | [[Category: Dehydrogenase]]
| + | |
| - | [[Category: Nadp]]
| + | |
| - | [[Category: Oxidoreductase]]
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