7n80: Difference between revisions
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<StructureSection load='7n80' size='340' side='right'caption='[[7n80]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='7n80' size='340' side='right'caption='[[7n80]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7n80]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[7n80]] 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=7N80 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N80 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</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=7n80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n80 OCA], [https://pdbe.org/7n80 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n80 RCSB], [https://www.ebi.ac.uk/pdbsum/7n80 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n80 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=7n80 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n80 OCA], [https://pdbe.org/7n80 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n80 RCSB], [https://www.ebi.ac.uk/pdbsum/7n80 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n80 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/PI42B_HUMAN PI42B_HUMAN] Participates in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.<ref>PMID:9038203</ref> | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Chen | [[Category: Chen S]] | ||
[[Category: Ha | [[Category: Ha Y]] | ||
Latest revision as of 18:22, 4 October 2023
Crystal Structure of PI5P4KIIBetaCrystal Structure of PI5P4KIIBeta
Structural highlights
FunctionPI42B_HUMAN Participates in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.[1] Publication Abstract from PubMedMost human cancer cells harbor loss-of-function mutations in the p53 tumor suppressor gene. Genetic experiments have shown that phosphatidylinositol 5-phosphate 4-kinase alpha and beta (PI5P4Kalpha and PI5P4Kbeta) are essential for the development of late-onset tumors in mice with germline p53 deletion, but the mechanism underlying this acquired dependence remains unclear. PI5P4K has been previously implicated in metabolic regulation. Here, we show that inhibition of PI5P4Kalpha/beta kinase activity by a potent and selective small-molecule probe disrupts cell energy homeostasis, causing AMPK activation and mTORC1 inhibition in a variety of cell types. Feedback through the S6K/insulin receptor substrate (IRS) loop contributes to insulin hypersensitivity and enhanced PI3K signaling in terminally differentiated myotubes. Most significantly, the energy stress induced by PI5P4Kalphabeta inhibition is selectively toxic toward p53-null tumor cells. The chemical probe, and the structural basis for its exquisite specificity, provide a promising platform for further development, which may lead to a novel class of diabetes and cancer drugs. Pharmacological inhibition of PI5P4Kalpha/beta disrupts cell energy metabolism and selectively kills p53-null tumor cells.,Chen S, Chandra Tjin C, Gao X, Xue Y, Jiao H, Zhang R, Wu M, He Z, Ellman J, Ha Y Proc Natl Acad Sci U S A. 2021 May 25;118(21). pii: 2002486118. doi:, 10.1073/pnas.2002486118. PMID:34001596[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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