1t2v | pdb_00001t2v

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File:1t2v.gif


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1t2v, resolution 3.30Å
Ligands: SEP
Gene: BRCA1 (Homo sapiens)
Related: 1JNX, 1N5O, 1T2U


Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Structural basis of phospho-peptide recognition by the BRCT domain of BRCA1, structure with phosphopeptide


Overview

The BRCT repeats in BRCA1 are essential for its tumor suppressor activity and interact with phosphorylated protein targets containing the sequence pSer-X-X-Phe, where X indicates any residue. The structure of the tandem BRCA1 BRCT repeats bound to an optimized phosphopeptide reveals that the N-terminal repeat harbors a conserved BRCT phosphoserine-binding pocket, while the interface between the repeats forms a hydrophobic groove that recognizes the phenylalanine. Crystallographic and biochemical data suggest that the structural integrity of both binding sites is essential for peptide recognition. The diminished peptide-binding capacity observed for cancer-associated BRCA1-BRCT variants may explain the enhanced cancer risks associated with these mutations.

Disease

Known disease associated with this structure: Breast cancer-1 OMIM:[113705], Breast-ovarian cancer OMIM:[113705], Ovarian cancer OMIM:[113705], Papillary serous carcinoma of the peritoneum OMIM:[113705]

About this Structure

1T2V is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1., Williams RS, Lee MS, Hau DD, Glover JN, Nat Struct Mol Biol. 2004 Jun;11(6):519-25. Epub 2004 May 9. PMID:15133503

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