2cn5
From Proteopedia
CRYSTAL STRUCTURE OF HUMAN CHK2 IN COMPLEX WITH ADP
Overview
The protein kinase Chk2 (checkpoint kinase 2) is a major effector of the replication checkpoint. Chk2 activation is initiated by phosphorylation of Thr68, in the serine-glutamine/threonine-glutamine cluster domain (SCD), by ATM. The phosphorylated SCD-segment binds to the FHA domain of a second Chk2 molecule, promoting dimerisation of the protein and triggering phosphorylation of the activation segment/T-loop in the kinase domain. We have now determined the structure of the kinase domain of human Chk2 in complexes with ADP and a small-molecule inhibitor debromohymenialdisine. The structure reveals a remarkable dimeric arrangement in which T-loops are exchanged between protomers, to form an active kinase conformation in trans. Biochemical data suggest that this dimer is the biologically active state promoted by ATM-phosphorylation, and also suggests a mechanism for dimerisation-driven activation of Chk2 by trans-phosphorylation.
About this Structure
2CN5 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Trans-activation of the DNA-damage signalling protein kinase Chk2 by T-loop exchange., Oliver AW, Paul A, Boxall KJ, Barrie SE, Aherne GW, Garrett MD, Mittnacht S, Pearl LH, EMBO J. 2006 Jul 12;25(13):3179-90. Epub 2006 Jun 22. PMID:16794575 Page seeded by OCA on Sat May 3 22:33:53 2008
Categories: Homo sapiens | Non-specific serine/threonine protein kinase | Single protein | Oliver, A W. | Pearl, L H. | Activation segment | Alternative splicing | Atp-binding | Cancer | Cds1 | Cell cycle | Checkpoint | Chek2 | Chk2 | Disease mutation | Kinase | Kinase domain | Li-fraumeni syndrome | Magnesium | Metal-binding | Nuclear protein | Nucleotide-binding | Phosphorylation | Proto-oncogene | Rad53 | Serine/threonine-protein kinase | Transferase | Tumour suppressor
