4E93
Crystal structure of human Feline Sarcoma Viral Oncogene Homologue (v-FES)in complex with TAE684
Summary for 4E93
| Entry DOI | 10.2210/pdb4e93/pdb |
| Related | 3BKB |
| Descriptor | Tyrosine-protein kinase Fes/Fps, 5-CHLORO-N-[2-METHOXY-4-[4-(4-METHYLPIPERAZIN-1-YL)PIPERIDIN-1-YL]PHENYL]-N'-(2-PROPAN-2-YLSULFONYLPHENYL)PYRIMIDINE-2,4-DIAMINE (3 entities in total) |
| Functional Keywords | v-fes, fujinami, avian sarcoma, viral, oncogene, feline sarcoma virus, atp-binding, kinase, nucleotide-binding, phosphoprotein, proto-oncogene, sh2 domain, transferase, tyrosine-protein kinase, transferase-transferase inhibitor complex, structural genomics, structural genomics consortium, sgc, transferase/transferase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm, cytosol: P07332 |
| Total number of polymer chains | 1 |
| Total formula weight | 43372.24 |
| Authors | Filippakopoulos, P.,Salah, E.,Miduturu, C.V.,Fedorov, O.,Cooper, C.,von Delft, F.,Arrowsmith, C.H.,Edwards, A.M.,Weigelt, J.,Gray, N.S.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2012-03-20, release date: 2012-04-18, Last modification date: 2023-09-13) |
| Primary citation | Hellwig, S.,Miduturu, C.V.,Kanda, S.,Zhang, J.,Filippakopoulos, P.,Salah, E.,Deng, X.,Choi, H.G.,Zhou, W.,Hur, W.,Knapp, S.,Gray, N.S.,Smithgall, T.E. Small-Molecule Inhibitors of the c-Fes Protein-Tyrosine Kinase. Chem.Biol., 19:529-540, 2012 Cited by PubMed Abstract: The c-Fes protein-tyrosine kinase modulates cellular signaling pathways governing differentiation, the innate immune response, and vasculogenesis. Here, we report the identification of types I and II kinase inhibitors with potent activity against c-Fes both in vitro and in cell-based assays. One of the most potent inhibitors is the previously described anaplastic lymphoma kinase inhibitor TAE684. The crystal structure of TAE684 in complex with the c-Fes SH2-kinase domain showed excellent shape complementarity with the ATP-binding pocket and a key role for the gatekeeper methionine in the inhibitory mechanism. TAE684 and two pyrazolopyrimidines with nanomolar potency against c-Fes in vitro were used to establish a role for this kinase in osteoclastogenesis, illustrating the value of these inhibitors as tool compounds to probe the diverse biological functions associated with this unique kinase. PubMed: 22520759DOI: 10.1016/j.chembiol.2012.01.020 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.84 Å) |
Structure validation
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