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| | <StructureSection load='5hpe' size='340' side='right'caption='[[5hpe]], [[Resolution|resolution]] 2.27Å' scene=''> | | <StructureSection load='5hpe' size='340' side='right'caption='[[5hpe]], [[Resolution|resolution]] 2.27Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5hpe]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://proteopedia.org/fgij/fg.htm?mol=5HPE FirstGlance]. <br> | + | <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='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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.27Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDC37 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] </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=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> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5hpe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hpe OCA], [http://pdbe.org/5hpe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hpe RCSB], [http://www.ebi.ac.uk/pdbsum/5hpe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hpe ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Phosphoprotein phosphatase]]
| + | [[Category: Mariotti L]] |
| - | [[Category: Mariotti, L]] | + | [[Category: Oberoi J]] |
| - | [[Category: Oberoi, J]] | + | [[Category: Vaughan C]] |
| - | [[Category: Vaughan, C]] | + | |
| - | [[Category: Enzyme]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Phosphatase domain]]
| + | |
| - | [[Category: Phosphorylation]]
| + | |
| - | [[Category: Substrate]]
| + | |
| Structural highlights
Function
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.[1] 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.
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.
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Stepanova L, Leng X, Parker SB, Harper JW. Mammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4. Genes Dev. 1996 Jun 15;10(12):1491-502. PMID:8666233
- ↑ Oberoi J, Dunn DM, Woodford MR, Mariotti L, Schulman J, Bourboulia D, Mollapour M, Vaughan CK. Structural and functional basis of protein phosphatase 5 substrate specificity. Proc Natl Acad Sci U S A. 2016 Jul 27. pii: 201603059. PMID:27466404 doi:http://dx.doi.org/10.1073/pnas.1603059113
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