4C36
PKA-S6K1 Chimera with compound 15e (CCT147581) bound
Summary for 4C36
| Entry DOI | 10.2210/pdb4c36/pdb |
| Related | 4C33 4C34 4C35 4C37 4C38 |
| Descriptor | CAMP-DEPENDENT PROTEIN KINASE CATALYTIC SUBUNIT ALPHA, CAMP-DEPENDENT PROTEIN KINASE INHIBITOR ALPHA, 4-[1-(cyclopropylmethyl)-1H-benzimidazol-2-yl]-1,2,5-oxadiazol-3-amine, ... (5 entities in total) |
| Functional Keywords | transferase-inhibitor complex, chimera, s6k1, transferase/inhibitor |
| Biological source | BOS TAURUS (BOVINE) More |
| Total number of polymer chains | 2 |
| Total formula weight | 43542.37 |
| Authors | Couty, S.,Westwood, I.M.,Kalusa, A.,Cano, C.,Travers, J.,Boxall, K.,Chow, C.L.,Burns, S.,Schmitt, J.,Pickard, L.,Barillari, C.,McAndrew, P.C.,Clarke, P.A.,Linardopoulos, S.,Griffin, R.J.,Aherne, G.W.,Raynaud, F.I.,Workman, P.,Jones, K.,van Montfort, R.L.M. (deposition date: 2013-08-21, release date: 2013-10-09, Last modification date: 2024-10-16) |
| Primary citation | Couty, S.,Westwood, I.M.,Kalusa, A.,Cano, C.,Travers, J.,Boxall, K.,Chow, C.L.,Burns, S.,Schmitt, J.,Pickard, L.,Barillari, C.,McAndrew, P.C.,Clarke, P.A.,Linardopoulos, S.,Griffin, R.J.,Aherne, G.W.,Raynaud, F.I.,Workman, P.,Jones, K.,van Montfort, R.L. The discovery of potent ribosomal S6 kinase inhibitors by high-throughput screening and structure-guided drug design. Oncotarget, 4:1647-1661, 2013 Cited by PubMed Abstract: The ribosomal P70 S6 kinases play a crucial role in PI3K/mTOR regulated signalling pathways and are therefore potential targets for the treatment of a variety of diseases including diabetes and cancer. In this study we describe the identification of three series of chemically distinct S6K1 inhibitors. In addition, we report a novel PKA-S6K1 chimeric protein with five mutations in or near its ATP-binding site, which was used to determine the binding mode of two of the three inhibitor series, and provided a robust system to aid the optimisation of the oxadiazole-substituted benzimidazole inhibitor series. We show that the resulting oxadiazole-substituted aza-benzimidazole is a potent and ligand efficient S6 kinase inhibitor, which blocks the phosphorylation of RPS6 at Ser235/236 in TSC negative HCV29 human bladder cancer cells by inhibiting S6 kinase activity and thus provides a useful tool compound to investigate the function of S6 kinases. PubMed: 24072592DOI: 10.18632/oncotarget.1255 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.98 Å) |
Structure validation
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