6MYN
Crystal structure of murine NF-kappaB inducing kinase (NIK) bound to inhibitor R7
Summary for 6MYN
| Entry DOI | 10.2210/pdb6myn/pdb |
| Related | 4G3C |
| Descriptor | Mitogen-activated protein kinase kinase kinase 14, SULFATE ION, (5s,7s)-9-fluoro-10-[(3R)-3-hydroxy-3-(5-methyl-1,2-oxazol-3-yl)but-1-yn-1-yl]-N~3~-methyl-6,7-dihydro-5H-5,7-methanoimidazo[2,1-a][2]benzazepine-2,3-dicarboxamide, ... (4 entities in total) |
| Functional Keywords | nik, kinase, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Mus musculus (Mouse) |
| Total number of polymer chains | 2 |
| Total formula weight | 78205.88 |
| Authors | Harris, S.F.,Smith, M.,Barker, J. (deposition date: 2018-11-01, release date: 2019-08-07, Last modification date: 2024-03-13) |
| Primary citation | Feng, J.A.,Lee, P.,Alaoui, M.H.,Barrett, K.,Castanedo, G.,Godemann, R.,McEwan, P.,Wang, X.,Wu, P.,Zhang, Y.,Harris, S.F.,Staben, S.T. Structure Based Design of Potent Selective Inhibitors of Protein Kinase D1 (PKD1). Acs Med.Chem.Lett., 10:1260-1265, 2019 Cited by PubMed Abstract: We previously disclosed a series of type I 1/2 inhibitors of NF-κB inducing kinase (NIK). Inhibition of NIK by these compounds was found to be strongly dependent on the inclusion and absolute stereochemistry of a propargyl tertiary alcohol as it forms critical hydrogen bonds (H-bonds) with NIK. We report that inhibition of protein kinase D1 (PKD1) by this class of compounds is not dependent on H-bond interactions of this tertiary alcohol. This feature was leveraged in the design of highly selective inhibitors of PKD1 that no longer inhibit NIK. A structure-based hypothesis based on the position and flexibility of the α-C-helix of PKD1 vs NIK is presented. PubMed: 31531194DOI: 10.1021/acsmedchemlett.8b00658 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.744 Å) |
Structure validation
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