5vdk
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of human WEE2 kinase domain in complex with MK1775== | |
| + | <StructureSection load='5vdk' size='340' side='right' caption='[[5vdk]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5vdk]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VDK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VDK FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8X7:1-[6-(2-hydroxypropan-2-yl)pyridin-2-yl]-6-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-2-(prop-2-en-1-yl)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one'>8X7</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vc3|5vc3]], [[5vc4|5vc4]], [[5vc5|5vc5]], [[5vd2|5vd2]], [[5vc6|5vc6]], [[5vd9|5vd9]], [[5vd8|5vd8]], [[5vd7|5vd7]], [[5vd5|5vd5]], [[5vd4|5vd4]], [[5vda|5vda]]</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5vdk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vdk OCA], [http://pdbe.org/5vdk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vdk RCSB], [http://www.ebi.ac.uk/pdbsum/5vdk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vdk ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/WEE2_HUMAN WEE2_HUMAN]] Oocyte-specific protein tyrosine kinase that phosphorylates and inhibits CDK1 and acts as a key regulator of meiosis during both prophase I and metaphase II. Required to maintain meiotic arrest in oocytes during the germinal vesicle (GV) stage, a long period of quiescence at dictyate prophase I, by phosphorylating CDK1 at 'Tyr-15', leading to inhibit CDK1 activity and prevent meiotic reentry. Also required for metaphase II exit during egg activation by phosphorylating CDK1 at 'Tyr-15', to ensure exit from meiosis in oocytes and promote pronuclear formation (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Members of the Wee family of kinases negatively regulate the cell cycle via phosphorylation of CDK1 and are considered potential drug targets. Herein, we investigated the structure-function relationship of human Wee1, Wee2 and Myt1 (PKMYT1). Purified recombinant full-length proteins and kinase domain constructs differed substantially in phosphorylation states and catalytic competency suggesting complex mechanisms of activation. A series of crystal structures revealed unique features that distinguish Wee1 and Wee2 from Myt1 and establish the structural basis of differential inhibition by the widely used Wee1 inhibitor MK-1775. Kinome profiling and cellular studies demonstrate that, in addition to Wee1 and Wee2, MK-1775 is an equally potent inhibitor of the polo-like kinase PLK1. Several previously unrecognized inhibitors of Wee kinases were discovered and characterized. Combined, the data provide a comprehensive view on the catalytic and structural properties of Wee kinases and a framework for the rational design of novel inhibitors thereof. | ||
| - | + | Structural basis of Wee kinases functionality and inactivation by diverse small molecule inhibitors.,Zhu JY, Cuellar RAD, Berndt N, Lee HE, Olesen SH, Martin MP, Jensen JT, Georg GI, Schonbrunn E J Med Chem. 2017 Aug 9. doi: 10.1021/acs.jmedchem.7b00996. PMID:28792760<ref>PMID:28792760</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5vdk" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Non-specific protein-tyrosine kinase]] | ||
| + | [[Category: Schonbrunn, E]] | ||
| + | [[Category: Zhu, J Y]] | ||
| + | [[Category: Cell cycle]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Kinase domain]] | ||
| + | [[Category: Transferase]] | ||
| + | [[Category: Transferase-transferase inhibitor complex]] | ||
| + | [[Category: Wee2]] | ||
Revision as of 11:13, 24 August 2017
Crystal structure of human WEE2 kinase domain in complex with MK1775
| |||||||||||
