5VD1
CRYSTAL STRUCTURE OF HUMAN MYT1 KINASE DOMAIN IN COMPLEX WITH PHA-848125
Summary for 5VD1
| Entry DOI | 10.2210/pdb5vd1/pdb |
| Related | 5VCV 5VCW 5VCX 5VCY 5VCZ 5VD0 5VD3 |
| Descriptor | Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase, N,1,4,4-TETRAMETHYL-8-{[4-(4-METHYLPIPERAZIN-1-YL)PHENYL]AMINO}-4,5-DIHYDRO-1H-PYRAZOLO[4,3-H]QUINAZOLINE-3-CARBOXAMIDE, DI(HYDROXYETHYL)ETHER, ... (4 entities in total) |
| Functional Keywords | kinase domain, cell cycle, tyrosine- and threonine-specific kinase, membrane-associated protein kinase, transferase, inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 35064.83 |
| Authors | Zhu, J.-Y.,Schonbrunn, E. (deposition date: 2017-04-01, release date: 2017-08-23, Last modification date: 2023-10-04) |
| Primary citation | Zhu, J.Y.,Cuellar, R.A.,Berndt, N.,Lee, H.E.,Olesen, S.H.,Martin, M.P.,Jensen, J.T.,Georg, G.I.,Schonbrunn, E. Structural Basis of Wee Kinases Functionality and Inactivation by Diverse Small Molecule Inhibitors. J. Med. Chem., 60:7863-7875, 2017 Cited by PubMed Abstract: 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 reveal 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. PubMed: 28792760DOI: 10.1021/acs.jmedchem.7b00996 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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