2cn8

File:2cn8.gif

spinqualitylabelsall models 2cn8, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

CRYSTAL STRUCTURE OF HUMAN CHK2 IN COMPLEX WITH DEBROMOHYMENIALDISINE

OverviewOverview

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 StructureAbout this Structure

2CN8 is a Single protein structure of sequence from Homo sapiens with MG, NO3 and DBQ as ligands. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Structure known Active Site: AC1. Full crystallographic information is available from OCA.

ReferenceReference

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

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