5WVD
Structure of Mnk1 in complex with DS12881479
Summary for 5WVD
| Entry DOI | 10.2210/pdb5wvd/pdb |
| Related | 5WVJ 5WVL |
| Descriptor | MAP kinase interacting serine/threonine kinase 1, SULFATE ION, 1-methyl-N-(5-phenyl-1,3-thiazol-2-yl)piperidine-4-carboxamide (3 entities in total) |
| Functional Keywords | kinase, kinase inhibitor, inactive conformation, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 70189.81 |
| Authors | Matsui, Y.,Hanzawa, H. (deposition date: 2016-12-24, release date: 2018-01-03, Last modification date: 2023-11-22) |
| Primary citation | Matsui, Y.,Yasumatsu, I.,Yoshida, K.I.,Iimura, S.,Ikeno, Y.,Nawano, T.,Fukano, H.,Ubukata, O.,Hanzawa, H.,Tanzawa, F.,Isoyama, T. A novel inhibitor stabilizes the inactive conformation of MAPK-interacting kinase 1. Acta Crystallogr F Struct Biol Commun, 74:156-160, 2018 Cited by PubMed Abstract: Mitogen-activated protein kinase (MAPK)-interacting kinases 1 (Mnk1) and 2 (Mnk2) modulate translation initiation through the phosphorylation of eukaryotic translation initiation factor 4E, which promotes tumorigenesis. However, Mnk1 and Mnk2 are dispensable in normal cells, suggesting that the inhibition of Mnk1 and Mnk2 could be effective in cancer therapy. To provide a structural basis for Mnk1 inhibition, a novel Mnk1 inhibitor was discovered and the crystal structure of Mnk1 in complex with this inhibitor was determined. The crystal structure revealed that the inhibitor binds to the autoinhibited state of Mnk1, stabilizing the Mnk-specific DFD motif in the DFD-out conformation, thus preventing Mnk1 from switching to the active conformation and thereby inhibiting the kinase activity. These results provide a valuable platform for the structure-guided design of Mnk1 inhibitors. PubMed: 29497019DOI: 10.1107/S2053230X18002108 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3 Å) |
Structure validation
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