Structural insights into mouse anti-apoptotic Bcl-xl reveal affinity for Beclin 1 and gossypol

Amit Priyadarshi, Ankoor Roy, Key Sun Kim, Eunice Eun Kyeong Kim, Kwang Yeon Hwang

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


This study reports the crystal structures of Bcl-xl wild type and three Bcl-xl mutants (Y101A, F105A, and R139A) with amino acid substitutions in the hydrophobic groove of the Bcl-xl BH3 domain. An additional 12 ordered residues were observed in a highly flexible loop between the α1 and α2 helices, and were recognized as an important deamidation site for the regulation of apoptosis. The autophagy-effector protein, Beclin 1, contains a novel BH3 domain (residues 101-125), which binds to the surface cleft of Bcl-xl, as confirmed by nuclear magnetic resonance (NMR) spectroscopy and analytical gel-filtration results. Gossypol, a potent inhibitor of Bcl-xl, had a Kd value of 0.9 μM. In addition, the structural and biochemical analysis of five Bcl-xl substitution mutants will provide structural insights into the design and development of anti-cancer drugs.

Original languageEnglish
Pages (from-to)515-521
Number of pages7
JournalBiochemical and biophysical research communications
Issue number3
Publication statusPublished - 2010 Apr 9


  • Apoptosis
  • Bcl-xl
  • Beclin
  • Gossypol
  • Mutation

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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