6YG0
Crystal structure of S287D,T291D MKK7 (MAP2K7), apo form
Summary for 6YG0
| Entry DOI | 10.2210/pdb6yg0/pdb |
| Descriptor | Dual specificity mitogen-activated protein kinase kinase 7 (2 entities in total) |
| Functional Keywords | kinase, kinase inhibitor, mkk7, mek7, map2k7, map2k, mek, jnk signaling, structural genomics, structural genomics consortium, sgc, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 34986.61 |
| Authors | Chaikuad, A.,Knapp, S.,Structural Genomics Consortium (SGC) (deposition date: 2020-03-27, release date: 2020-08-12, Last modification date: 2024-01-24) |
| Primary citation | Schroder, M.,Tan, L.,Wang, J.,Liang, Y.,Gray, N.S.,Knapp, S.,Chaikuad, A. Catalytic Domain Plasticity of MKK7 Reveals Structural Mechanisms of Allosteric Activation and Diverse Targeting Opportunities. Cell Chem Biol, 27:1285-1295.e4, 2020 Cited by PubMed Abstract: MKK7 (MEK7) is a key regulator of the JNK stress signaling pathway and targeting MKK7 has been proposed as a chemotherapeutic strategy. Detailed understanding of the MKK7 structure and factors that affect its activity is therefore of critical importance. Here, we present a comprehensive set of MKK7 crystal structures revealing insights into catalytic domain plasticity and the role of the N-terminal regulatory helix, conserved in all MAP2Ks, mediating kinase activation. Crystal structures harboring this regulatory helix revealed typical structural features of active kinase, providing exclusively a first model of the MAP2K active state. A small-molecule screening campaign yielded multiple scaffolds, including type II irreversible inhibitors a binding mode that has not been reported previously. We also observed an unprecedented allosteric pocket located in the N-terminal lobe for the approved drug ibrutinib. Collectively, our structural and functional data expand and provide alternative targeting strategies for this important MAP2K kinase. PubMed: 32783966DOI: 10.1016/j.chembiol.2020.07.014 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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