7po7
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7po7]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PO7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PO7 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7po7]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7PO7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7PO7 FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.31Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7po7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7po7 OCA], [https://pdbe.org/7po7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7po7 RCSB], [https://www.ebi.ac.uk/pdbsum/7po7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7po7 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=7po7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7po7 OCA], [https://pdbe.org/7po7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7po7 RCSB], [https://www.ebi.ac.uk/pdbsum/7po7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7po7 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | [https://www.uniprot.org/uniprot/PGP_MOUSE PGP_MOUSE] Glycerol-3-phosphate phosphatase hydrolyzing glycerol-3-phosphate into glycerol. Thereby, regulates the cellular levels of glycerol-3-phosphate a metabolic intermediate of glucose, lipid and energy metabolism (PubMed:26755581). Was also shown to have a 2-phosphoglycolate phosphatase activity and a tyrosine-protein phosphatase activity. However, their physiological relevance is unclear (PubMed: | + | [https://www.uniprot.org/uniprot/PGP_MOUSE PGP_MOUSE] Glycerol-3-phosphate phosphatase hydrolyzing glycerol-3-phosphate into glycerol. Thereby, regulates the cellular levels of glycerol-3-phosphate a metabolic intermediate of glucose, lipid and energy metabolism (PubMed:26755581). Was also shown to have a 2-phosphoglycolate phosphatase activity and a tyrosine-protein phosphatase activity. However, their physiological relevance is unclear (PubMed:24338473, PubMed:26755581). In vitro, has also a phosphatase activity toward ADP, ATP, GDP and GTP (PubMed:24338473).<ref>PMID:24338473</ref> <ref>PMID:26755581</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Targeting the intrinsic metabolism of immune or tumor cells is a therapeutic strategy in autoimmunity, chronic inflammation or cancer. Metabolite repair enzymes may represent an alternative target class for selective metabolic inhibition, but pharmacological tools to test this concept are needed. Here, we demonstrate that phosphoglycolate phosphatase (PGP), a prototypical metabolite repair enzyme in glycolysis, is a pharmacologically actionable target. Using a combination of small molecule screening, protein crystallography, molecular dynamics simulations and NMR metabolomics, we discover and analyze a compound (CP1) that inhibits PGP with high selectivity and submicromolar potency. CP1 locks the phosphatase in a catalytically inactive conformation, dampens glycolytic flux, and phenocopies effects of cellular PGP-deficiency. This study provides key insights into effective and precise PGP targeting, at the same time validating an allosteric approach to control glycolysis that could advance discoveries of innovative therapeutic candidates. | ||
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| + | Glycolytic flux control by drugging phosphoglycolate phosphatase.,Jeanclos E, Schlotzer J, Hadamek K, Yuan-Chen N, Alwahsh M, Hollmann R, Fratz S, Yesilyurt-Gerhards D, Frankenbach T, Engelmann D, Keller A, Kaestner A, Schmitz W, Neuenschwander M, Hergenroder R, Sotriffer C, von Kries JP, Schindelin H, Gohla A Nat Commun. 2022 Nov 11;13(1):6845. doi: 10.1038/s41467-022-34228-2. PMID:36369173<ref>PMID:36369173</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7po7" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Phosphoglycolate phosphatase from Mus musculus
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