title: Structure-activity relationship studies to probe the phosphoprotein binding site on the carboxy terminal domains of the breast cancer susceptibility gene 1.
abstract: Carboxy terminal BRCT domains of the breast cancer susceptibility gene 1 (BRCA1) bind to phosphorylated proteins through a pSXXF consensus recognition motif. We report a systematic structure-activity relationship study that maps the BRCT(BRCA1)-pSXXF binding interface, leading to identification of peptides with nanomolar binding affinities comparable to those of the previously reported 13-mer peptides and providing a clear description of the pSXXF-BRCT interface, which is essential for developing small molecule inhibitors via the peptidomimetic approach.
authors.affiliation: Eppley Institute for Cancer Research and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States.
authors.forename: Ziyan
authors.initials: Z
authors.lastname: Yuan
authors.forename: Eric A
authors.initials: EA
authors.lastname: Kumar
authors.forename: Smitha
authors.initials: S
authors.lastname: Kizhake
authors.forename: Amarnath
authors.initials: A
authors.lastname: Natarajan
mesh_terms: D019313:BRCA1 Protein / Q000737:chemistry*; D001665:Binding Sites; D002151:Calorimetry; D008958:Models, Molecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D010750:Phosphoproteins / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D019313:BRCA1 Protein; D009842:Oligopeptides; D010750:Phosphoproteins