2cn5
From Proteopedia
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|PDB= 2cn5 |SIZE=350|CAPTION= <scene name='initialview01'>2cn5</scene>, resolution 2.25Å | |PDB= 2cn5 |SIZE=350|CAPTION= <scene name='initialview01'>2cn5</scene>, resolution 2.25Å | ||
|SITE= <scene name='pdbsite=AC1:Adp+Binding+Site+For+Chain+A'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Adp+Binding+Site+For+Chain+A'>AC1</scene> | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=ADP:ADENOSINE-5'-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</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] | + | |ACTIVITY= <span class='plainlinks'>[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] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2cn5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2cn5 OCA], [http://www.ebi.ac.uk/pdbsum/2cn5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2cn5 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Breast and colorectal cancer, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604373 604373]], Breast cancer, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604373 604373]], Li-Fraumeni syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604373 604373]], Osteosarcoma, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604373 604373]], Prostate cancer, familial OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604373 604373]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Oliver, A W.]] | [[Category: Oliver, A W.]] | ||
[[Category: Pearl, L H.]] | [[Category: Pearl, L H.]] | ||
| - | [[Category: ADP]] | ||
| - | [[Category: CL]] | ||
| - | [[Category: MG]] | ||
| - | [[Category: NO3]] | ||
[[Category: activation segment]] | [[Category: activation segment]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
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[[Category: tumour suppressor]] | [[Category: tumour suppressor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:23:52 2008'' |
Revision as of 23:23, 30 March 2008
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| , resolution 2.25Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , , | ||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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 Mon Mar 31 02:23:52 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
