5hpe: Difference between revisions

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-'''Unreleased structure'''
-The entry 5hpe is ON HOLD
+==Phosphatase domain of PP5 bound to a phosphomimetic Cdc37 substrate peptide==
+<StructureSection load='5hpe' size='340' side='right'caption='[[5hpe]], [[Resolution|resolution]] 2.27&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5hpe]] 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=5HPE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HPE 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]] 2.27&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NCO:COBALT+HEXAMMINE(III)'>NCO</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=5hpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hpe OCA], [https://pdbe.org/5hpe PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hpe RCSB], [https://www.ebi.ac.uk/pdbsum/5hpe PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hpe ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/CDC37_HUMAN CDC37_HUMAN] Co-chaperone that binds to numerous kinases and promotes their interaction with the Hsp90 complex, resulting in stabilization and promotion of their activity.<ref>PMID:8666233</ref> [https://www.uniprot.org/uniprot/PPP5_HUMAN PPP5_HUMAN] May play a role in the regulation of RNA biogenesis and/or mitosis. In vitro, dephosphorylates serine residues of skeletal muscle phosphorylase and histone H1.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The serine/threonine phosphatase protein phosphatase 5 (PP5) regulates hormone- and stress-induced cellular signaling by association with the molecular chaperone heat shock protein 90 (Hsp90). PP5-mediated dephosphorylation of the cochaperone Cdc37 is essential for activation of Hsp90-dependent kinases. However, the details of this mechanism remain unknown. We determined the crystal structure of a Cdc37 phosphomimetic peptide bound to the catalytic domain of PP5. The structure reveals PP5 utilization of conserved elements of phosphoprotein phosphatase (PPP) structure to bind substrate and provides a template for many PPP-substrate interactions. Our data show that, despite a highly conserved structure, elements of substrate specificity are determined within the phosphatase catalytic domain itself. Structure-based mutations in vivo reveal that PP5-mediated dephosphorylation is required for kinase and steroid hormone receptor release from the chaperone complex. Finally, our data show that hyper- or hypoactivity of PP5 mutants increases Hsp90 binding to its inhibitor, suggesting a mechanism to enhance the efficacy of Hsp90 inhibitors by regulation of PP5 activity in tumors.
-Authors: Oberoi, J., Mariotti, L., Vaughan, C.
+Structural and functional basis of protein phosphatase 5 substrate specificity.,Oberoi J, Dunn DM, Woodford MR, Mariotti L, Schulman J, Bourboulia D, Mollapour M, Vaughan CK Proc Natl Acad Sci U S A. 2016 Jul 27. pii: 201603059. PMID:27466404<ref>PMID:27466404</ref>
-Description: Phosphatase domain of PP5 bound to a phosphomimetic Cdc37 substrate peptide
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Oberoi, J]]
+<div class="pdbe-citations 5hpe" style="background-color:#fffaf0;"></div>
-[[Category: Mariotti, L]]
-[[Category: Vaughan, C]]
+==See Also==
+*[[Protein phosphatase 3D structures|Protein phosphatase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Mariotti L]]
+[[Category: Oberoi J]]
+[[Category: Vaughan C]]