1gxc
From Proteopedia
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|PDB= 1gxc |SIZE=350|CAPTION= <scene name='initialview01'>1gxc</scene>, resolution 2.70Å | |PDB= 1gxc |SIZE=350|CAPTION= <scene name='initialview01'>1gxc</scene>, resolution 2.70Å | ||
|SITE= <scene name='pdbsite=TPB:Tpo+Binding+Site+For+Chain+K'>TPB</scene> | |SITE= <scene name='pdbsite=TPB:Tpo+Binding+Site+For+Chain+K'>TPB</scene> | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1gxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1gxc OCA], [http://www.ebi.ac.uk/pdbsum/1gxc PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1gxc RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The Chk2 Ser/Thr kinase plays crucial, evolutionarily conserved roles in cellular responses to DNA damage. Identification of two pro-oncogenic mutations within the Chk2 FHA domain has highlighted its importance for Chk2 function in checkpoint activation. The X-ray structure of the Chk2 FHA domain in complex with an in vitro selected phosphopeptide motif reveals the determinants of binding specificity and shows that both mutations are remote from the peptide binding site. We show that the Chk2 FHA domain mediates ATM-dependent Chk2 phosphorylation and targeting of Chk2 to in vivo binding partners such as BRCA1 through either or both of two structurally distinct mechanisms. Although phospho-dependent binding is important for Chk2 activity, previously uncharacterized phospho-independent FHA domain interactions appear to be the primary target of oncogenic lesions. | The Chk2 Ser/Thr kinase plays crucial, evolutionarily conserved roles in cellular responses to DNA damage. Identification of two pro-oncogenic mutations within the Chk2 FHA domain has highlighted its importance for Chk2 function in checkpoint activation. The X-ray structure of the Chk2 FHA domain in complex with an in vitro selected phosphopeptide motif reveals the determinants of binding specificity and shows that both mutations are remote from the peptide binding site. We show that the Chk2 FHA domain mediates ATM-dependent Chk2 phosphorylation and targeting of Chk2 to in vivo binding partners such as BRCA1 through either or both of two structurally distinct mechanisms. Although phospho-dependent binding is important for Chk2 activity, previously uncharacterized phospho-independent FHA domain interactions appear to be the primary target of oncogenic lesions. | ||
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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: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:53:24 2008'' |
Revision as of 17:53, 30 March 2008
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| , resolution 2.70Å | |||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
FHA DOMAIN FROM HUMAN CHK2 KINASE IN COMPLEX WITH A SYNTHETIC PHOSPHOPEPTIDE
Overview
The Chk2 Ser/Thr kinase plays crucial, evolutionarily conserved roles in cellular responses to DNA damage. Identification of two pro-oncogenic mutations within the Chk2 FHA domain has highlighted its importance for Chk2 function in checkpoint activation. The X-ray structure of the Chk2 FHA domain in complex with an in vitro selected phosphopeptide motif reveals the determinants of binding specificity and shows that both mutations are remote from the peptide binding site. We show that the Chk2 FHA domain mediates ATM-dependent Chk2 phosphorylation and targeting of Chk2 to in vivo binding partners such as BRCA1 through either or both of two structurally distinct mechanisms. Although phospho-dependent binding is important for Chk2 activity, previously uncharacterized phospho-independent FHA domain interactions appear to be the primary target of oncogenic lesions.
About this Structure
1GXC is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2., Li J, Williams BL, Haire LF, Goldberg M, Wilker E, Durocher D, Yaffe MB, Jackson SP, Smerdon SJ, Mol Cell. 2002 May;9(5):1045-54. PMID:12049740
Page seeded by OCA on Sun Mar 30 20:53:24 2008
