Structural characterization of BRCT-tetrapeptide binding interactions

Prem Raj B. Joseph, Ziyan Yuan, Eric A. Kumar, G. L. Lokesh, Smitha Kizhake, Krishna Rajarathnam, Amarnath Natarajan

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


BRCT(BRCA1) plays a major role in DNA repair pathway, and does so by recognizing the conserved sequence pSXXF in its target proteins. Remarkably, tetrapeptides containing pSXXF motif bind with high specificity and micromolar affinity. Here, we have characterized the binding interactions of pSXXF tetrapeptides using NMR spectroscopy and calorimetry. We show that BRCT is dynamic and becomes structured on binding, that pSer and Phe residues dictate overall binding, and that the binding affinities of the tetrapeptides are intimately linked to structural and dynamic changes both in the BRCT(BRCA1) and tetrapeptides. These results provide critical insights for designing high-affinity BRCT(BRCA1) inhibitors.

Original languageEnglish (US)
Pages (from-to)207-210
Number of pages4
JournalBiochemical and Biophysical Research Communications
Issue number2
StatePublished - Mar 5 2010
Externally publishedYes


  • NMR
  • Structure
  • Thermodynamics
  • pSXXF tetrapeptide

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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