4i6f

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{{STRUCTURE_4i6f| PDB=4i6f | SCENE= }}
 
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===Selective & Brain-Permeable Polo-like Kinase-2 (Plk-2) Inhibitors that Reduce -Synuclein Phosphorylation in Rat Brain===
 
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{{ABSTRACT_PUBMED_23794260}}
 
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==Function==
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==Selective & Brain-Permeable Polo-like Kinase-2 (Plk-2) Inhibitors that Reduce -Synuclein Phosphorylation in Rat Brain==
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[[http://www.uniprot.org/uniprot/PLK2_HUMAN PLK2_HUMAN]] Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition. Polo-like kinases act by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates CENPJ, NPM1, RAPGEF2, RASGRF1, SNCA, SIPA1L1 and SYNGAP1. Plays a key role in synaptic plasticity and memory by regulating the Ras and Rap protein signaling: required for overactivity-dependent spine remodeling by phosphorylating the Ras activator RASGRF1 and the Rap inhibitor SIPA1L1 leading to their degradation by the proteasome. Conversely, phosphorylates the Rap activator RAPGEF2 and the Ras inhibitor SYNGAP1, promoting their activity. Also regulates synaptic plasticity independently of kinase activity, via its interaction with NSF that disrupts the interaction between NSF and the GRIA2 subunit of AMPARs, leading to a rapid rundown of AMPAR-mediated current that occludes long term depression. Required for procentriole formation and centriole duplication by phosphorylating CENPJ and NPM1, respectively. Its induction by p53/TP53 suggests that it may participate in the mitotic checkpoint following stress.<ref>PMID:15242618</ref> <ref>PMID:19001868</ref> <ref>PMID:20531387</ref> <ref>PMID:20352051</ref>
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<StructureSection load='4i6f' size='340' side='right'caption='[[4i6f]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4i6f]] 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=4I6F OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I6F FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1C7:(7R)-8-CYCLOPENTYL-7-ETHYL-5-METHYL-2-(2-PHENYL-1H-IMIDAZOL-1-YL)-7,8-DIHYDROPTERIDIN-6(5H)-ONE'>1C7</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4i6f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i6f OCA], [https://pdbe.org/4i6f PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i6f RCSB], [https://www.ebi.ac.uk/pdbsum/4i6f PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i6f ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PLK2_HUMAN PLK2_HUMAN] Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition. Polo-like kinases act by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates CENPJ, NPM1, RAPGEF2, RASGRF1, SNCA, SIPA1L1 and SYNGAP1. Plays a key role in synaptic plasticity and memory by regulating the Ras and Rap protein signaling: required for overactivity-dependent spine remodeling by phosphorylating the Ras activator RASGRF1 and the Rap inhibitor SIPA1L1 leading to their degradation by the proteasome. Conversely, phosphorylates the Rap activator RAPGEF2 and the Ras inhibitor SYNGAP1, promoting their activity. Also regulates synaptic plasticity independently of kinase activity, via its interaction with NSF that disrupts the interaction between NSF and the GRIA2 subunit of AMPARs, leading to a rapid rundown of AMPAR-mediated current that occludes long term depression. Required for procentriole formation and centriole duplication by phosphorylating CENPJ and NPM1, respectively. Its induction by p53/TP53 suggests that it may participate in the mitotic checkpoint following stress.<ref>PMID:15242618</ref> <ref>PMID:19001868</ref> <ref>PMID:20531387</ref> <ref>PMID:20352051</ref>
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==About this Structure==
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==See Also==
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[[4i6f]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I6F OCA].
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*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:023794260</ref><references group="xtra"/><references/>
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__TOC__
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[[Category: Polo kinase]]
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</StructureSection>
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[[Category: Pan, H.]]
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[[Category: Homo sapiens]]
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[[Category: Kinase inhibitor]]
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[[Category: Large Structures]]
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[[Category: Parkinsons disease]]
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[[Category: Pan H]]
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[[Category: Synuclein]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

Selective & Brain-Permeable Polo-like Kinase-2 (Plk-2) Inhibitors that Reduce -Synuclein Phosphorylation in Rat Brain

PDB ID 4i6f

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