5WI2
Crystal structure of the KA1 domain from human Chk1
Summary for 5WI2
| Entry DOI | 10.2210/pdb5wi2/pdb |
| Descriptor | cDNA FLJ56409, highly similar to Serine/threonine-protein kinase Chk1 (EC 2.7.11.1), ACETATE ION, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | kinase, checkpoint, autoinhibition, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 24336.42 |
| Authors | Emptage, R.P.,Marmorstein, R. (deposition date: 2017-07-18, release date: 2017-10-04, Last modification date: 2024-11-06) |
| Primary citation | Emptage, R.P.,Schoenberger, M.J.,Ferguson, K.M.,Marmorstein, R. Intramolecular autoinhibition of checkpoint kinase 1 is mediated by conserved basic motifs of the C-terminal kinase-associated 1 domain. J. Biol. Chem., 292:19024-19033, 2017 Cited by PubMed Abstract: Precise control of the cell cycle allows for timely repair of genetic material prior to replication. One factor intimately involved in this process is checkpoint kinase 1 (Chk1), a DNA damage repair inducing Ser/Thr protein kinase that contains an N-terminal kinase domain and a C-terminal regulatory region consisting of a ∼100-residue linker followed by a putative kinase-associated 1 (KA1) domain. We report the crystal structure of the human Chk1 KA1 domain, demonstrating striking structural homology with other sequentially diverse KA1 domains. Separately purified Chk1 kinase and KA1 domains are intimately associated in solution, which results in inhibition of Chk1 kinase activity. Using truncation mutants and site-directed mutagenesis, we define the inhibitory face of the KA1 domain as a series of basic residues residing on two conserved regions of the primary structure. These findings point to KA1-mediated intramolecular autoinhibition as a key regulatory mechanism of human Chk1, and provide new therapeutic possibilities with which to attack this validated oncology target with small molecules. PubMed: 28972186DOI: 10.1074/jbc.M117.811265 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.495 Å) |
Structure validation
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