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1wsx

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[[Image:1wsx.gif|left|200px]]
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{{STRUCTURE_1wsx| PDB=1wsx | SCENE= }}
{{STRUCTURE_1wsx| PDB=1wsx | SCENE= }}
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'''Solution structure of MCL-1'''
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===Solution structure of MCL-1===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_15550399}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 15550399 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15550399}}
==About this Structure==
==About this Structure==
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1WSX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WSX OCA].
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1WSX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WSX OCA].
==Reference==
==Reference==
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[[Category: Helical bundle]]
[[Category: Helical bundle]]
[[Category: Mcl-1]]
[[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 Jul 28 08:01:01 2008''

Revision as of 05:01, 28 July 2008

Image:1wsx.png

Template:STRUCTURE 1wsx

Solution structure of MCL-1

Template:ABSTRACT PUBMED 15550399

About this Structure

1WSX is a Single protein structure of sequence from Mus musculus. Full experimental 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

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