3IHC

Crystal structure of mouse Bcl-xl (wt) at pH 5.0

Summary for 3IHC

• Entry DOI: 10.2210/pdb3ihc/pdb
• Related: 3IHD 3IHE 3IHF 3IHG 3IIG 3IIH
• Descriptor: Bcl-2-like protein 1 (2 entities in total)
• Functional Keywords: apoptosis, bh3 domain, bcl-2, membrane, mitochondrion, transmembrane
• Biological source: Mus musculus (mouse)
• Cellular location: Mitochondrion membrane; Single-pass membrane protein. Isoform Bcl-X(L): Mitochondrion inner membrane. Isoform Bcl-X(delta-TM): Cytoplasm: Q64373
• Total number of polymer chains: 1
• Total formula weight: 22056.21

Authors

Priyadarshi, A.,Hwang, K.Y. (deposition date: 2009-07-30, release date: 2010-04-14, Last modification date: 2023-11-01)

Primary citation

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., 394:515-521, 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

Experimental method

X-RAY DIFFRACTION (1.85 Å)