4QO9
MST3 IN COMPLEX WITH Danusertib
Summary for 4QO9
| Entry DOI | 10.2210/pdb4qo9/pdb |
| Related | 4QML 4QMM 4QMN 4QMO 4QMP 4QMQ 4QMS 4QMT 4QMU 4QMV 4QMW 4QMX 4QMY 4QMZ |
| Descriptor | SERINE/THREONINE-PROTEIN KINASE 24, TRIETHYLENE GLYCOL, 1,2-ETHANEDIOL, ... (7 entities in total) |
| Functional Keywords | protein kinase, mst3, stk24, sterile 20-like kinase, atp-binding, nucleotide-binding, phosphoprotein, serine/threonine-transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm: Q9Y6E0 |
| Total number of polymer chains | 2 |
| Total formula weight | 71535.05 |
| Authors | Olesen, S.H.,Watts, C.,Zhu, J.-Y.,Schonbrunn, E. (deposition date: 2014-06-19, release date: 2015-07-29, Last modification date: 2024-11-06) |
| Primary citation | Olesen, S.H.,Zhu, J.Y.,Martin, M.P.,Schonbrunn, E. Discovery of Diverse Small-Molecule Inhibitors of Mammalian Sterile20-like Kinase 3 (MST3). Chemmedchem, 11:1137-1144, 2016 Cited by PubMed Abstract: Increasing evidence suggests key roles for members of the mammalian Sterile20-like (MST) family of kinases in many aspects of biology. MST3 is a member of the STRIPAK complex, the deregulation of which has recently been associated with cancer cell migration and metastasis. Targeting MST3 with small-molecule inhibitors may be beneficial for the treatment of certain cancers, but little information exists on the potential of kinase inhibitor scaffolds to engage with MST3. In this study we screened MST3 against a library of 277 kinase inhibitors using differential scanning fluorimetry and confirmed 14 previously unknown MST3 inhibitors by X-ray crystallography. These compounds, of which eight are in clinical trials or FDA approved, comprise nine distinct chemical scaffolds that inhibit MST3 enzymatic activity with IC50 values between 0.003 and 23 μm. The structure-activity relationships explain the differential inhibitory activity of these compounds against MST3 and the structural basis for high binding potential, the information of which may serve as a framework for the rational design of MST3-selective inhibitors as potential therapeutics and to interrogate the function of this enzyme in diseased cells. PubMed: 27135311DOI: 10.1002/cmdc.201600115 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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