View source for 4b6l


==Discovery of Oral Polo-Like Kinase (PLK) Inhibitors with Enhanced Selectivity Profile using Residue Targeted Drug Design==
<StructureSection load='4b6l' size='340' side='right'caption='[[4b6l]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4b6l]] 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=4B6L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B6L 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=9ZP:4-[[(4R)-5-CYCLOPENTYL-4-ETHYL-3A,4-DIHYDRO-3H-[1,2,4]TRIAZOLO[4,3-F]PTERIDIN-7-YL]AMINO]-N-CYCLOPROPYL-3-METHOXY-BENZAMIDE'>9ZP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4b6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b6l OCA], [https://pdbe.org/4b6l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b6l RCSB], [https://www.ebi.ac.uk/pdbsum/4b6l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b6l ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PLK3_HUMAN PLK3_HUMAN] Serine/threonine-protein kinase involved in cell cycle regulation, response to stress and Golgi disassembly. Polo-like kinases act by binding and phosphorylating proteins are that already phosphorylated on a specific motif recognized by the POLO box domains. Phosphorylates ATF2, BCL2L1, CDC25A, CDC25C, CHEK2, HIF1A, JUN, p53/TP53, p73/TP73, PTEN, TOP2A and VRK1. Involved in cell cycle regulation: required for entry into S phase and cytokinesis. Phosphorylates BCL2L1, leading to regulate the G2 checkpoint and progression to cytokinesis during mitosis. Plays a key role in response to stress: rapidly activated upon stress stimulation, such as ionizing radiation, reactive oxygen species (ROS), hyperosmotic stress, UV irradiation and hypoxia. Involved in DNA damage response and G1/S transition checkpoint by phosphorylating CDC25A, p53/TP53 and p73/TP73. Phosphorylates p53/TP53 in response to reactive oxygen species (ROS), thereby promoting p53/TP53-mediated apoptosis. Phosphorylates CHEK2 in response to DNA damage, promoting the G2/M transition checkpoint. Phosphorylates the transcription factor p73/TP73 in response to DNA damage, leading to inhibit p73/TP73-mediated transcriptional activation and pro-apoptotic functions. Phosphorylates HIF1A and JUN is response to hypoxia. Phosphorylates ATF2 following hyperosmotic stress in corneal epithelium. Also involved in Golgi disassembly during the cell cycle: part of a MEK1/MAP2K1-dependent pathway that induces Golgi fragmentation during mitosis by mediating phosphorylation of VRK1. May participate in endomitotic cell cycle, a form of mitosis in which both karyokinesis and cytokinesis are interrupted and is a hallmark of megakaryocyte differentiation, via its interaction with CIB1.<ref>PMID:12242661</ref> <ref>PMID:9353331</ref> <ref>PMID:10557092</ref> <ref>PMID:11156373</ref> <ref>PMID:11447225</ref> <ref>PMID:11551930</ref> <ref>PMID:11971976</ref> <ref>PMID:14980500</ref> <ref>PMID:14968113</ref> <ref>PMID:15021912</ref> <ref>PMID:16478733</ref> <ref>PMID:16481012</ref> <ref>PMID:17804415</ref> <ref>PMID:17264206</ref> <ref>PMID:18062778</ref> <ref>PMID:18650425</ref> <ref>PMID:19490146</ref> <ref>PMID:19103756</ref> <ref>PMID:20889502</ref> <ref>PMID:20940307</ref> <ref>PMID:21098032</ref> <ref>PMID:21840391</ref> <ref>PMID:21376736</ref> <ref>PMID:21264284</ref> 

==See Also==
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Brown K]]
[[Category: Charrier JD]]
[[Category: Durrant S]]
[[Category: Griffiths M]]
[[Category: Hudson C]]
[[Category: Kay D]]
[[Category: Knegtel R]]
[[Category: ODonnell M]]
[[Category: Pierard F]]
[[Category: Twin H]]
[[Category: Weber P]]
[[Category: Young S]]