7MYX
Crystal structure of the PH domain (R86A) of Akt1
Summary for 7MYX
| Entry DOI | 10.2210/pdb7myx/pdb |
| Descriptor | RAC-alpha serine/threonine-protein kinase (2 entities in total) |
| Functional Keywords | kinase, signaling protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 14456.34 |
| Authors | Bae, H.,Park, E.,Cole, P.A.,Eck, M.J. (deposition date: 2021-05-22, release date: 2022-11-09, Last modification date: 2023-10-18) |
| Primary citation | Bae, H.,Viennet, T.,Park, E.,Chu, N.,Salguero, A.,Eck, M.J.,Arthanari, H.,Cole, P.A. PH domain-mediated autoinhibition and oncogenic activation of Akt. Elife, 11:-, 2022 Cited by PubMed Abstract: Akt is a Ser/Thr protein kinase that plays a central role in metabolism and cancer. Regulation of Akt's activity involves an autoinhibitory intramolecular interaction between its pleckstrin homology (PH) domain and its kinase domain that can be relieved by C-tail phosphorylation. PH domain mutant E17K Akt is a well-established oncogene. Previously, we reported that the conformation of autoinhibited Akt may be shifted by small molecule allosteric inhibitors limiting the mechanistic insights from existing X-ray structures that have relied on such compounds (Chu et al., 2020). Here, we discover unexpectedly that a single mutation R86A Akt exhibits intensified autoinhibitory features with enhanced PH domain-kinase domain affinity. Structural and biochemical analysis uncovers the importance of a key interaction network involving Arg86, Glu17, and Tyr18 that controls Akt conformation and activity. Our studies also shed light on the molecular basis for E17K Akt activation as an oncogenic driver. PubMed: 35968932DOI: 10.7554/eLife.80148 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.39 Å) |
Structure validation
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