|
|
| Line 3: |
Line 3: |
| | <StructureSection load='5j0a' size='340' side='right'caption='[[5j0a]], [[Resolution|resolution]] 2.74Å' scene=''> | | <StructureSection load='5j0a' size='340' side='right'caption='[[5j0a]], [[Resolution|resolution]] 2.74Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5j0a]] is a 2 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=5J0A OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5J0A FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5j0a]] 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=5J0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5J0A FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HC4:4-HYDROXYCINNAMIC+ACID'>HC4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.74Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PBK, TOPK ([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=HC4:4-HYDROXYCINNAMIC+ACID'>HC4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase Mitogen-activated protein kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.2 2.7.12.2] </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=5j0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j0a OCA], [https://pdbe.org/5j0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5j0a RCSB], [https://www.ebi.ac.uk/pdbsum/5j0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5j0a 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=5j0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5j0a OCA], [http://pdbe.org/5j0a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5j0a RCSB], [http://www.ebi.ac.uk/pdbsum/5j0a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5j0a ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TOPK_HUMAN TOPK_HUMAN]] Phosphorylates MAP kinase p38. Seems to be active only in mitosis. May also play a role in the activation of lymphoid cells. When phosphorylated, forms a complex with TP53, leading to TP53 destabilization and attenuation of G2/M checkpoint during doxorubicin-induced DNA damage.<ref>PMID:10781613</ref> <ref>PMID:17482142</ref> | + | [https://www.uniprot.org/uniprot/TOPK_HUMAN TOPK_HUMAN] Phosphorylates MAP kinase p38. Seems to be active only in mitosis. May also play a role in the activation of lymphoid cells. When phosphorylated, forms a complex with TP53, leading to TP53 destabilization and attenuation of G2/M checkpoint during doxorubicin-induced DNA damage.<ref>PMID:10781613</ref> <ref>PMID:17482142</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 24: |
Line 23: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mitogen-activated protein kinase kinase]]
| + | [[Category: Yang X]] |
| - | [[Category: Yang, X]] | + | [[Category: Zhou H]] |
| - | [[Category: Zhou, H]] | + | [[Category: Zou QW]] |
| - | [[Category: Zou, Q W]] | + | |
| - | [[Category: Protein kinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
TOPK_HUMAN Phosphorylates MAP kinase p38. Seems to be active only in mitosis. May also play a role in the activation of lymphoid cells. When phosphorylated, forms a complex with TP53, leading to TP53 destabilization and attenuation of G2/M checkpoint during doxorubicin-induced DNA damage.[1] [2]
Publication Abstract from PubMed
The overexpression of PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) has been associated with hematologic tumors, breast cancer and various other cancers. However, the three-dimensional structure of PBK has not been solved. In this study, we determined the crystal structure of human PBK, which has two phospho-mimicking mutations T9E and T198E. The structural data indicated that PBK may assemble into an inactive dimer in alkaline conditions. Analytical size-exclusion chromatography and analytical ultracentrifugation confirmed that PBK exists in a conformational transition between dimers and monomers at different pH conditions. Co-IP and kinase assays suggested that the active state of PBK is a monomer and does not form a dimer even under alkaline conditions. These results showed that the conformational transition of PBK is important for its kinase activity regulation. Collectively, our observations may provide a novel starting point for structure-based functional studies.
The crystal structure of an inactive dimer of PDZ-binding kinase.,Dong C, Tang X, Xie Y, Zou Q, Yang X, Zhou H Biochem Biophys Res Commun. 2016 Aug 5;476(4):586-93. doi:, 10.1016/j.bbrc.2016.05.166. Epub 2016 Jun 1. PMID:27262437[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Abe Y, Matsumoto S, Kito K, Ueda N. Cloning and expression of a novel MAPKK-like protein kinase, lymphokine-activated killer T-cell-originated protein kinase, specifically expressed in the testis and activated lymphoid cells. J Biol Chem. 2000 Jul 14;275(28):21525-31. PMID:10781613 doi:http://dx.doi.org/10.1074/jbc.M909629199
- ↑ Nandi AK, Ford T, Fleksher D, Neuman B, Rapoport AP. Attenuation of DNA damage checkpoint by PBK, a novel mitotic kinase, involves protein-protein interaction with tumor suppressor p53. Biochem Biophys Res Commun. 2007 Jun 22;358(1):181-8. Epub 2007 Apr 30. PMID:17482142 doi:http://dx.doi.org/S0006-291X(07)00824-8
- ↑ Dong C, Tang X, Xie Y, Zou Q, Yang X, Zhou H. The crystal structure of an inactive dimer of PDZ-binding kinase. Biochem Biophys Res Commun. 2016 Aug 5;476(4):586-93. doi:, 10.1016/j.bbrc.2016.05.166. Epub 2016 Jun 1. PMID:27262437 doi:http://dx.doi.org/10.1016/j.bbrc.2016.05.166
|
