5np8: Difference between revisions

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5np8 is ON HOLD
+==PGK1 in complex with CRT0063465 (3-[2-(4-bromophenyl)-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin-6-yl]propanoic acid)==
+<StructureSection load='5np8' size='340' side='right'caption='[[5np8]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5np8]] 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=5NP8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NP8 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]] 1.9&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PG:3-PHOSPHOGLYCERIC+ACID'>3PG</scene>, <scene name='pdbligand=93T:3-[2-(4-bromophenyl)-5,7-dimethyl-pyrazolo[1,5-a]pyrimidin-6-yl]propanoic+acid'>93T</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=5np8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5np8 OCA], [https://pdbe.org/5np8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5np8 RCSB], [https://www.ebi.ac.uk/pdbsum/5np8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5np8 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/PGK1_HUMAN PGK1_HUMAN] Defects in PGK1 are the cause of phosphoglycerate kinase 1 deficiency (PGK1D) [MIM:[https://omim.org/entry/300653 300653]. It is a condition with a highly variable clinical phenotype that includes hemolytic anemia, rhabdomyolysis, myopathy and neurologic involvement. Patients can express one or more of these manifestations.<ref>PMID:8673469</ref> <ref>PMID:8043870</ref> <ref>PMID:8615693</ref> <ref>PMID:9744480</ref> <ref>PMID:2001457</ref> <ref>PMID:1586722</ref> <ref>PMID:1547346</ref> <ref>PMID:6941312</ref> <ref>PMID:6933565</ref>
+== Function ==
+[https://www.uniprot.org/uniprot/PGK1_HUMAN PGK1_HUMAN] In addition to its role as a glycolytic enzyme, it seems that PGK-1 acts as a polymerase alpha cofactor protein (primer recognition protein).
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Telomere signaling and metabolic dysfunction are hallmarks of cell aging. New agents targeting these processes might provide therapeutic opportunities, including chemoprevention strategies against cancer predisposition. We report identification and characterization of a pyrazolopyrimidine compound series identified from screens focused on cell immortality and whose targets are glycolytic kinase PGK1 and oxidative stress sensor DJ1. We performed structure-activity studies on the series to develop a photoaffinity probe to deconvolute the cellular targets. In vitro binding and structural analyses confirmed these targets, suggesting that PGK1/DJ1 interact, which we confirmed by immunoprecipitation. Glucose homeostasis and oxidative stress are linked to telomere signaling and exemplar compound CRT0063465 blocked hypoglycemic telomere shortening. Intriguingly, PGK1 and DJ1 bind to TRF2 and telomeric DNA. Compound treatment modulates these interactions and also affects Shelterin complex composition, while conferring cellular protection from cytotoxicity due to bleomycin and desferroxamine. These results demonstrate therapeutic potential of the compound series.
-Authors:
+A Novel Pyrazolopyrimidine Ligand of Human PGK1 and Stress Sensor DJ1 Modulates the Shelterin Complex and Telomere Length Regulation.,Bilsland AE, Liu Y, Turnbull A, Sumpton D, Stevenson K, Cairney CJ, Boyd SM, Roffey J, Jenkinson D, Keith WN Neoplasia. 2019 Aug 8;21(9):893-907. doi: 10.1016/j.neo.2019.07.008. PMID:31401411<ref>PMID:31401411</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5np8" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Phosphoglycerate kinase 3D structures|Phosphoglycerate kinase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Bilsland AE]]
+[[Category: Cairney CJ]]
+[[Category: Jenkinson D]]
+[[Category: Keith WN]]
+[[Category: Liu Y]]
+[[Category: Roffey J]]
+[[Category: Stevenson K]]
+[[Category: Sumpton D]]
+[[Category: Turnbull AP]]