2cn5

(Difference between revisions)

Revision as of 14:17, 20 March 2008

Image:2cn5.gif

, 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

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

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Retrieved from "http://52.214.119.220/wiki/index.php/2cn5"

@@ Line 1: / Line 1: @@
-[[Image:2cn5.gif|left|200px]]<br /><applet load="2cn5" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:2cn5.gif|left|200px]]
-caption="2cn5, resolution 2.25&Aring;" />
-'''CRYSTAL STRUCTURE OF HUMAN CHK2 IN COMPLEX WITH ADP'''<br />
+ {{Structure
+|PDB= 2cn5 |SIZE=350|CAPTION= <scene name='initialview01'>2cn5</scene>, resolution 2.25&Aring;
+|SITE= <scene name='pdbsite=AC1:Adp+Binding+Site+For+Chain+A'>AC1</scene>
+|LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene> and <scene name='pdbligand=ADP:ADENOSINE-5'-DIPHOSPHATE'>ADP</scene>
+|ACTIVITY= [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1]
+|GENE=
+}}
+'''CRYSTAL STRUCTURE OF HUMAN CHK2 IN COMPLEX WITH ADP'''
 ==Overview==
@@ Line 10: / Line 19: @@
 ==About this Structure==
-CN5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=NO3:'>NO3</scene> and <scene name='pdbligand=ADP:'>ADP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Known structural/functional Site: <scene name='pdbsite=AC1:Adp+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CN5 OCA].
+CN5 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2CN5 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16794575 16794575]
+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:[http://www.ncbi.nlm.nih.gov/pubmed/16794575 16794575]
 [[Category: Homo sapiens]]
 [[Category: Non-specific serine/threonine protein kinase]]
@@ Line 47: / Line 56: @@
 [[Category: tumour suppressor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:50:23 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:17:29 2008''