Priyadarshi, Amit Roy, Ankoor Kim, Key Sun Kim, Eunice EunKyeong Hwang, Kwang Yeon 2024-01-20T19:33:07Z 2024-01-20T19:33:07Z 2021-09-02 2010-04 0006-291X https://pubs.kist.re.kr/handle/201004/131591 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 alpha 1 and alpha 2 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 K-d value of 0 9 mu M 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 (C) 2010 Elsevier Inc All rights reserved English Academic Press Structural insights into mouse anti-apoptotic Bcl-xl reveal affinity for Beclin 1 and gossypol Article 10.1016/j.bbrc.2010.03.002 1 Biochemical and Biophysical Research Communications, v.394, no.3, pp.515 - 521 Biochemical and Biophysical Research Communications 394 3 515 521 N scie scopus 000276785900015 2-s2.0-77950518734 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article CRYSTAL-STRUCTURE PEPTIDE COMPLEX REGULATORS BCL-X(L) RAY Bcl-xl Beclin Apoptosis Gossypol Mutation