7AKM

Crystal structure of CHK1 kinase domain in complex with ATPyS

Summary for 7AKM

• Entry DOI: 10.2210/pdb7akm/pdb
• Descriptor: Serine/threonine-protein kinase Chk1, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: cell cycle
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 69773.34

Authors

Day, M.,Oliver, A.W.,Pearl, L.H. (deposition date: 2020-10-01, release date: 2021-04-14, Last modification date: 2024-01-31)

Primary citation

Day, M.,Parry-Morris, S.,Houghton-Gisby, J.,Oliver, A.W.,Pearl, L.H.
Structural basis for recruitment of the CHK1 DNA damage kinase by the CLASPIN scaffold protein.
Structure, 29:531-, 2021

PubMed Abstract: CHK1 is a protein kinase that functions downstream of activated ATR to phosphorylate multiple targets as part of intra-S and G2/M DNA damage checkpoints. Its role in allowing cells to survive replicative stress has made it an important target for anti-cancer drug discovery. Activation of CHK1 by ATR depends on their mutual interaction with CLASPIN, a natively unstructured protein that interacts with CHK1 through a cluster of phosphorylation sites in its C-terminal half. We have now determined the crystal structure of the kinase domain of CHK1 bound to a high-affinity motif from CLASPIN. Our data show that CLASPIN engages a conserved site on CHK1 adjacent to the substrate-binding cleft, involved in phosphate sensing in other kinases. The CLASPIN motif is not phosphorylated by CHK1, nor does it affect phosphorylation of a CDC25 substrate peptide, suggesting that it functions purely as a scaffold for CHK1 activation by ATR.

PubMed: 33789090
DOI: 10.1016/j.str.2021.03.007

Experimental method

X-RAY DIFFRACTION (1.93 Å)