2nte
From Proteopedia
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Crystal Structure of the BARD1 BRCT Domains
Overview
The interaction of the breast tumor suppressor BRCA1 with the protein, BARD1 results in the formation of a heterodimeric complex that has, ubiquitin ligase activity and plays central roles in cell cycle checkpoint, control and DNA repair. Both BRCA1 and BARD1 possess a pair of tandem BRCT, domains that interact in a phosphorylation-dependent manner with target, proteins. We determined the crystal structure of the human BARD1 BRCT, repeats (residues 568-777) at 1.9 A resolution. The composition and, structure of the BARD1 phosphoserine-binding pocket P1 are strikingly, similar to those of the BRCA1 and MDC1 BRCT domains, suggesting a similar, mode of interaction with the phosphate group of the ligand. By contrast, the BARD1 BRCT selectivity pocket P2 exhibits distinct structural, features, including two prominent histidine residues, His685 and His686, which may be important for ligand binding. The protonation state of these, histidines has a marked effect on the calculated electrostatic potential, in the vicinity of P2, raising the possibility that ligand recognition may, be regulated by changes in pH. Importantly, the BARD1 BRCT structure, provides insights into the mechanisms by which the cancer-associated, missense mutations C645R, V695L, and S761N may adversely affect the, structure and function of BARD1.
About this Structure
2NTE is a Single protein structure of sequence from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure of the BARD1 BRCT domains., Birrane G, Varma AK, Soni A, Ladias JA, Biochemistry. 2007 Jul 3;46(26):7706-12. Epub 2007 Jun 6. PMID:17550235
Page seeded by OCA on Wed Jan 23 13:31:59 2008
Categories: Homo sapiens | Single protein | Birrane, G. | Ladias, J.A.A. | Soni, A. | Varma, A.K. | CL | EDO | SO4 | Brca1 | Brct | Ring finger | Ubiquitin ligase | Zinc-binding protein
