1R2G

Human Bcl-XL containing a Phe to Trp mutation at position 97

Summary for 1R2G

• Entry DOI: 10.2210/pdb1r2g/pdb
• Related: 1MAZ 1R2D 1R2E 1R2H 1R2I
• Descriptor: Apoptosis regulator Bcl-X (2 entities in total)
• Functional Keywords: apoptosis, monomeric, alpha-helical, mutation
• Biological source: Homo sapiens (human)
• Cellular location: Isoform Bcl-X(L): Mitochondrion inner membrane : Q07817
• Total number of polymer chains: 1
• Total formula weight: 24645.97

Authors

O'Neill, J.W.,Manion, M.K.,Giedt, C.D.,Kim, K.M.,Zhang, K.Y.,Hockenbery, D.M. (deposition date: 2003-09-26, release date: 2004-02-03, Last modification date: 2023-08-23)

Primary citation

Manion, M.K.,O'Neill, J.W.,Giedt, C.D.,Kim, K.M.,Zhang, K.Y.,Hockenbery, D.M.
Bcl-XL mutations suppress cellular sensitivity to antimycin A.
J.Biol.Chem., 279:2159-2165, 2004

PubMed Abstract: Cells expressing high levels of the BCL-X(L) anti-apoptotic protein are preferentially killed by the mitochondrial inhibitor antimycin A (AA). Computational modeling predicts a binding site for AA in the extended hydrophobic groove on BCL-X(L), previously identified as an interface for dimerization to BAX and related proapoptotic proteins. Here, we identify BCL-X(L) hydrophobic groove mutants with normal cellular anti-apoptotic function but suppressed sensitivity to AA. The LD(50) of AA for cells expressing BCL-X(L) mutants directly correlates with the measured in vitro dissociation constants for AA binding. These results indicate that BCL-X(L) is a principal target mediating AA cytotoxicity.

PubMed: 14534311
DOI: 10.1074/jbc.M306021200

Experimental method

X-RAY DIFFRACTION (2.7 Å)