1wsx

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[[Image:1wsx.gif|left|200px]]
[[Image:1wsx.gif|left|200px]]
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{{Structure
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|PDB= 1wsx |SIZE=350|CAPTION= <scene name='initialview01'>1wsx</scene>
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The line below this paragraph, containing "STRUCTURE_1wsx", creates the "Structure Box" on the page.
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|SITE=
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|GENE= mcl-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])
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{{STRUCTURE_1wsx| PDB=1wsx | SCENE= }}
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wsx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wsx OCA], [http://www.ebi.ac.uk/pdbsum/1wsx PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1wsx RCSB]</span>
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'''Solution structure of MCL-1'''
'''Solution structure of MCL-1'''
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[[Category: Huang, D C.]]
[[Category: Huang, D C.]]
[[Category: Richardson, S J.]]
[[Category: Richardson, S J.]]
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[[Category: apoptosis]]
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[[Category: Apoptosis]]
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[[Category: bcl-2]]
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[[Category: Bcl-2]]
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[[Category: bh3]]
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[[Category: Bh3]]
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[[Category: helical bundle]]
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[[Category: Helical bundle]]
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[[Category: mcl-1]]
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[[Category: Mcl-1]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 14:05:50 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:40:34 2008''
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Revision as of 11:05, 3 May 2008

Image:1wsx.gif

Template:STRUCTURE 1wsx

Solution structure of MCL-1


Overview

The B cell lymphoma-2 (Bcl-2) homologs myeloid cell leukemia-1 (Mcl-1) and A1 are prosurvival factors that selectively bind a subset of proapoptotic Bcl homology (BH) 3-only proteins. To investigate the molecular basis of the selectivity, we determined the solution structure of the C-terminal Bcl-2-like domain of Mcl-1. This domain shares features expected of a prosurvival Bcl-2 protein, having a helical fold centered on a core hydrophobic helix and a surface-exposed hydrophobic groove for binding its cognate partners. A number of residues in the binding groove differentiate Mcl-1 from its homologs, and in contrast to other Bcl-2 homologs, Mcl-1 has a binding groove in a conformation intermediate between the open structures characterized by peptide complexes and the closed state observed in unliganded structures. Mutagenesis of potential binding site residues was used to probe the contributions of groove residues to the binding properties of Mcl-1. Although mutations in Mcl-1 had little impact on binding, a single mutation in the BH3-only ligand Bad enabled it to bind both Mcl-1 and A1 while retaining its binding to Bcl-2, Bcl-xL, and Bcl-w. Elucidating the selective action of certain BH3-only ligands is required for delineating their mode of action and will aid the search for effective BH3-mimetic drugs.

About this Structure

1WSX is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

Reference

Solution structure of prosurvival Mcl-1 and characterization of its binding by proapoptotic BH3-only ligands., Day CL, Chen L, Richardson SJ, Harrison PJ, Huang DC, Hinds MG, J Biol Chem. 2005 Feb 11;280(6):4738-44. Epub 2004 Nov 18. PMID:15550399 Page seeded by OCA on Sat May 3 14:05:50 2008

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