1r2h

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(New page: 200px<br /> <applet load="1r2h" size="450" color="white" frame="true" align="right" spinBox="true" caption="1r2h, resolution 2.20&Aring;" /> '''Human Bcl-XL contai...)
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[[Image:1r2h.gif|left|200px]]<br />
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[[Image:1r2h.gif|left|200px]]<br /><applet load="1r2h" size="350" color="white" frame="true" align="right" spinBox="true"
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<applet load="1r2h" size="450" color="white" frame="true" align="right" spinBox="true"
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caption="1r2h, resolution 2.20&Aring;" />
caption="1r2h, resolution 2.20&Aring;" />
'''Human Bcl-XL containing an Ala to Leu mutation at position 142'''<br />
'''Human Bcl-XL containing an Ala to Leu mutation at position 142'''<br />
==Overview==
==Overview==
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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.
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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.
==About this Structure==
==About this Structure==
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1R2H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1R2H OCA].
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1R2H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R2H OCA].
==Reference==
==Reference==
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Giedt, C.D.]]
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[[Category: Giedt, C D.]]
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[[Category: Hockenbery, D.M.]]
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[[Category: Hockenbery, D M.]]
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[[Category: Kim, K.M.]]
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[[Category: Kim, K M.]]
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[[Category: Manion, M.K.]]
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[[Category: Manion, M K.]]
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[[Category: Neill, J.W.O.]]
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[[Category: Neill, J W.O.]]
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[[Category: Zhang, K.Y.]]
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[[Category: Zhang, K Y.]]
[[Category: alpha-helical]]
[[Category: alpha-helical]]
[[Category: apoptosis]]
[[Category: apoptosis]]
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[[Category: mutation]]
[[Category: mutation]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:59:03 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:46:22 2008''

Revision as of 12:46, 21 February 2008


1r2h, resolution 2.20Å

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Human Bcl-XL containing an Ala to Leu mutation at position 142

Overview

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.

About this Structure

1R2H is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Bcl-XL mutations suppress cellular sensitivity to antimycin A., Manion MK, O'Neill JW, Giedt CD, Kim KM, Zhang KY, Hockenbery DM, J Biol Chem. 2004 Jan 16;279(3):2159-65. Epub 2003 Oct 8. PMID:14534311

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