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5vd0
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==CRYSTAL STRUCTURE OF HUMAN MYT1 KINASE DOMAIN IN COMPLEX WITH MK1775== | |
| + | <StructureSection load='5vd0' size='340' side='right' caption='[[5vd0]], [[Resolution|resolution]] 2.13Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5vd0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VD0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VD0 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=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vcw|5vcw]], [[5vcx|5vcx]], [[5vcy|5vcy]], [[5vcz|5vcz]], [[5vd1|5vd1]], [[5vd3|5vd3]]</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_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </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=5vd0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vd0 OCA], [http://pdbe.org/5vd0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vd0 RCSB], [http://www.ebi.ac.uk/pdbsum/5vd0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vd0 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/PMYT1_HUMAN PMYT1_HUMAN]] Acts as a negative regulator of entry into mitosis (G2 to M transition) by phosphorylation of the CDK1 kinase specifically when CDK1 is complexed to cyclins. Mediates phosphorylation of CDK1 predominantly on 'Thr-14'. Also involved in Golgi fragmentation. May be involved in phosphorylation of CDK1 on 'Tyr-15' to a lesser degree, however tyrosine kinase activity is unclear and may be indirect. May be a downstream target of Notch signaling pathway during eye development.<ref>PMID:9001210</ref> <ref>PMID:10373560</ref> | ||
| + | <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 5vd0" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Non-specific serine/threonine protein kinase]] | ||
| + | [[Category: Schonbrunn, E]] | ||
| + | [[Category: Zhu, J Y]] | ||
| + | [[Category: Cell cycle]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Kinase domain]] | ||
| + | [[Category: Membrane-associated protein kinase]] | ||
| + | [[Category: Transferase]] | ||
| + | [[Category: Transferase-transferase inhibitor complex]] | ||
| + | [[Category: Tyrosine- and threonine-specific kinase]] | ||
Revision as of 10:59, 24 August 2017
CRYSTAL STRUCTURE OF HUMAN MYT1 KINASE DOMAIN IN COMPLEX WITH MK1775
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