3ILC

Crystal structure of mouse Bcl-xl mutant (Y101A) at pH 6.0

3ILC の概要

• エントリーDOI: 10.2210/pdb3ilc/pdb
• 関連するPDBエントリー: 3IHC 3IHD 3IHE 3IHF 3IIG 3IIH 3ILB
• 分子名称: Bcl-2-like protein 1 (2 entities in total)
• 機能のキーワード: apoptosis, bh3 domain, bcl-2, alternative splicing, cytoplasm, membrane, mitochondrion, transmembrane
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Isoform Bcl-X(L): Mitochondrion membrane. Isoform Bcl-X(delta-TM): Cytoplasm: Q64373
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 22102.26

構造登録者

Priyadarshi, A.,Hwang, K.Y. (登録日: 2009-08-07, 公開日: 2010-04-14, 最終更新日: 2023-11-01)

主引用文献

Priyadarshi, A.,Roy, A.,Kim, K.S.,Kim, E.E.,Hwang, K.Y.
Structural insights into mouse anti-apoptotic Bcl-xl reveal affinity for Beclin 1 and gossypol.
Biochem.Biophys.Res.Commun., 2010

PubMed Abstract: 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 alpha1 and alpha2 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 microM. 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.

PubMed: 20206602
DOI: 10.1016/j.bbrc.2010.03.002

実験手法

X-RAY DIFFRACTION (1.64 Å)