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3ihd

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Crystal structure of mouse Bcl-xl mutant (Y101A) at pH 5.0

Structural highlights

3ihd is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.88Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

B2CL1_MOUSE Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.^[1] Isoform Bcl-X(S) promotes apoptosis (By similarity).^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

Structural insights into mouse anti-apoptotic Bcl-xl reveal affinity for Beclin 1 and gossypol.,Priyadarshi A, Roy A, Kim KS, Kim EE, Hwang KY Biochem Biophys Res Commun. 2010 Apr 9;394(3):515-21. Epub 2010 Mar 4. PMID:20206602^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yang XF, Weber GF, Cantor H. A novel Bcl-x isoform connected to the T cell receptor regulates apoptosis in T cells. Immunity. 1997 Nov;7(5):629-39. PMID:9390687
↑ Yang XF, Weber GF, Cantor H. A novel Bcl-x isoform connected to the T cell receptor regulates apoptosis in T cells. Immunity. 1997 Nov;7(5):629-39. PMID:9390687
↑ Priyadarshi A, Roy A, Kim KS, Kim EE, Hwang KY. Structural insights into mouse anti-apoptotic Bcl-xl reveal affinity for Beclin 1 and gossypol. Biochem Biophys Res Commun. 2010 Apr 9;394(3):515-21. Epub 2010 Mar 4. PMID:20206602 doi:10.1016/j.bbrc.2010.03.002