2cn5

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spinqualitylabelsall models PDB ID 2cn5 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 2.25Å
Sites:
Ligands:	, , and
Activity:	Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Coordinates:	save as pdb, mmCIF, xml

CRYSTAL STRUCTURE OF HUMAN CHK2 IN COMPLEX WITH ADP

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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.

Disease

Known diseases associated with this structure: Breast and colorectal cancer, susceptibility to OMIM:[604373], Breast cancer, susceptibility to OMIM:[604373], Li-Fraumeni syndrome OMIM:[604373], Osteosarcoma, somatic OMIM:[604373], Prostate cancer, familial OMIM:[604373]

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 Thu Mar 20 16:17:29 2008