4gpz
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4gpz]] 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=4GPZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GPZ FirstGlance]. <br> | <table><tr><td colspan='2'>[[4gpz]] 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=4GPZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GPZ FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NEP:N1-PHOSPHONOHISTIDINE'>NEP</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]] 1.65Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NEP:N1-PHOSPHONOHISTIDINE'>NEP</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=4gpz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gpz OCA], [https://pdbe.org/4gpz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gpz RCSB], [https://www.ebi.ac.uk/pdbsum/4gpz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gpz 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=4gpz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gpz OCA], [https://pdbe.org/4gpz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gpz RCSB], [https://www.ebi.ac.uk/pdbsum/4gpz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gpz ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/PGAM1_HUMAN PGAM1_HUMAN] Interconversion of 3- and 2-phosphoglycerate with 2,3-bisphosphoglycerate as the primer of the reaction. Can also catalyze the reaction of EC 5.4.2.4 (synthase) and EC 3.1.3.13 (phosphatase), but with a reduced activity. | [https://www.uniprot.org/uniprot/PGAM1_HUMAN PGAM1_HUMAN] Interconversion of 3- and 2-phosphoglycerate with 2,3-bisphosphoglycerate as the primer of the reaction. Can also catalyze the reaction of EC 5.4.2.4 (synthase) and EC 3.1.3.13 (phosphatase), but with a reduced activity. | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | How oncogenic signalling coordinates glycolysis and anabolic biosynthesis in cancer cells remains unclear. We recently reported that the glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) regulates anabolic biosynthesis by controlling intracellular levels of its substrate 3-phosphoglycerate and product 2-phosphoglycerate. Here we report a novel mechanism in which Y26 phosphorylation enhances PGAM1 activation through release of inhibitory E19 that blocks the active site, stabilising cofactor 2,3-bisphosphoglycerate binding and H11 phosphorylation. We also report the crystal structure of H11-phosphorylated PGAM1 and find that phospho-H11 activates PGAM1 at least in part by promoting substrate 3-phosphoglycerate binding. Moreover, Y26 phosphorylation of PGAM1 is common in human cancer cells and contributes to regulation of 3-phosphoglycerate and 2-phosphoglycerate levels, promoting cancer cell proliferation and tumour growth. As PGAM1 is a negative transcriptional target of TP53, and is therefore commonly upregulated in human cancers, these findings suggest that Y26 phosphorylation represents an additional acute mechanism underlying phosphoglycerate mutase 1 upregulation. | ||
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| - | Tyr26 phosphorylation of PGAM1 provides a metabolic advantage to tumours by stabilizing the active conformation.,Hitosugi T, Zhou L, Fan J, Elf S, Zhang L, Xie J, Wang Y, Gu TL, Aleckovic M, Leroy G, Kang Y, Kang HB, Seo JH, Shan C, Jin P, Gong W, Lonial S, Arellano ML, Khoury HJ, Chen GZ, Shin DM, Khuri FR, Boggon TJ, Kang S, He C, Chen J Nat Commun. 2013;4:1790. doi: 10.1038/ncomms2759. PMID:23653202<ref>PMID:23653202</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4gpz" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
*[[Phosphoglycerate mutase 3D structures|Phosphoglycerate mutase 3D structures]] | *[[Phosphoglycerate mutase 3D structures|Phosphoglycerate mutase 3D structures]] | ||
| - | == References == | ||
| - | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Crystal structure of human B type phosphoglycerate mutase H11 phosphorylated form
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Categories: Homo sapiens | Large Structures | He C | Zhang L | Zhou L
