2cn8

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{{STRUCTURE_2cn8| PDB=2cn8 | SCENE= }}
{{STRUCTURE_2cn8| PDB=2cn8 | SCENE= }}
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'''CRYSTAL STRUCTURE OF HUMAN CHK2 IN COMPLEX WITH DEBROMOHYMENIALDISINE'''
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===CRYSTAL STRUCTURE OF HUMAN CHK2 IN COMPLEX WITH DEBROMOHYMENIALDISINE===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_16794575}}
==About this Structure==
==About this Structure==
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[[Category: Transferase]]
[[Category: Transferase]]
[[Category: Tumour suppressor]]
[[Category: Tumour suppressor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 22:34:03 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 01:57:09 2008''

Revision as of 22:57, 27 July 2008

Image:2cn8.png

Template:STRUCTURE 2cn8

CRYSTAL STRUCTURE OF HUMAN CHK2 IN COMPLEX WITH DEBROMOHYMENIALDISINE

Template:ABSTRACT PUBMED 16794575

About this Structure

2CN8 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

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