8SE2
Structure of Full-length Human Protein Kinase C Beta 1 (PKCBI) in the Active and Inactive Conformation Soaked in Manganese Chloride
Summary for 8SE2
| Entry DOI | 10.2210/pdb8se2/pdb |
| Related | 8SE1 |
| Descriptor | Protein kinase C beta type, GLYCEROL, ZINC ION, ... (7 entities in total) |
| Functional Keywords | protein kinase c beta, kinase, phosphorylation, pkcb, pkc, kinase signalling, prkcb, signaling protein, transferase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 155849.38 |
| Authors | Cong, A.T.Q.,Witter, T.L.,Bruinsma, E.S.,Jayaraman, S.,Hawse, J.R.,Goetz, M.P.,Schellenberg, M.J. (deposition date: 2023-04-07, release date: 2025-08-20, Last modification date: 2026-07-08) |
| Primary citation | Cong, A.T.Q.,Witter, T.L.,Bruinsma, E.S.,Sarkar Bhattacharya, S.,Jayaraman, S.,Wyatt, S.R.,Solverson, J.K.,Dugan, M.B.,Paluncic, J.,Kuffel, M.J.,Alvey, J.R.,Huynh, H.V.,Wu, X.,Fields, A.P.,Pandey, A.,Hawse, J.R.,Goetz, M.P.,Schellenberg, M.J. Molecular basis of allosteric regulation and pharmaceutical targeting of protein kinase C beta. Nat Commun, 2026 Cited by PubMed Abstract: Protein kinase C (PKC) isozymes are ubiquitous kinases that direct diverse cellular pathways and are important drug targets for the treatment of cancer and neurological diseases. PKCs are auto-regulating enzymes governed by phospholipid and Ca signals via a mechanism that has remained enigmatic due to a paucity of structural information. Herein we present a series of structures of the full-length human PKCβI and PKCβII isozymes. These structures reveal the molecular basis by which PKCs maintain an auto-inhibited state, convert to a defined and ordered active conformation via a "lipid-lever" mechanism of allosteric activation, and how isoform-specific differences alter their allosteric regulatory mechanisms. We show that endoxifen, a recently identified PKCβI inhibitor, can alter the allosteric regulatory mechanism of PKCβI, providing a proof of concept for allosteric regulators of PKCs. Collectively, our data describe a foundational molecular model of second messenger-mediated allosteric regulation of PKCs that underpins PKC function, misregulation, and mechanisms of inhibition. PubMed: 42168197DOI: 10.1038/s41467-026-73413-5 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.95 Å) |
Structure validation
Download full validation report
