6HHG
Crystal Structure of AKT1 in Complex with Covalent-Allosteric AKT Inhibitor 27
Summary for 6HHG
| Entry DOI | 10.2210/pdb6hhg/pdb |
| Descriptor | RAC-alpha serine/threonine-protein kinase, ~{N}-[2-chloranyl-5-[[1-[[4-(5-oxidanylidene-3-phenyl-6~{H}-1,6-naphthyridin-2-yl)phenyl]methyl]piperidin-4-yl]carbamoylamino]phenyl]propanamide (3 entities in total) |
| Functional Keywords | akt1, covalent-allosteric, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 52381.19 |
| Authors | Landel, I.,Weisner, J.,Mueller, M.P.,Scheinpflug, R.,Rauh, D. (deposition date: 2018-08-28, release date: 2019-02-20, Last modification date: 2024-10-23) |
| Primary citation | Uhlenbrock, N.,Smith, S.,Weisner, J.,Landel, I.,Lindemann, M.,Le, T.A.,Hardick, J.,Gontla, R.,Scheinpflug, R.,Czodrowski, P.,Janning, P.,Depta, L.,Quambusch, L.,Muller, M.P.,Engels, B.,Rauh, D. Structural and chemical insights into the covalent-allosteric inhibition of the protein kinase Akt. Chem Sci, 10:3573-3585, 2019 Cited by PubMed Abstract: The Ser/Thr kinase Akt (Protein Kinase B/PKB) is a master switch in cellular signal transduction pathways. Its downstream signaling influences cell proliferation, cell growth, and apoptosis, rendering Akt a prominent drug target. The unique activation mechanism of Akt involves a change of the relative orientation of its N-terminal pleckstrin homology (PH) and the kinase domain and makes this kinase suitable for highly specific allosteric modulation. Here we present a unique set of crystal structures of covalent-allosteric interdomain inhibitors in complex with full-length Akt and report the structure-based design, synthesis, biological and pharmacological evaluation of a focused library of these innovative inhibitors. PubMed: 30996949DOI: 10.1039/c8sc05212c PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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