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1n5o

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[[Image:1n5o.gif|left|200px]]<br /><applet load="1n5o" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1n5o.gif|left|200px]]
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caption="1n5o, resolution 2.80&Aring;" />
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'''Structural consequences of a cancer-causing BRCA1-BRCT missense mutation'''<br />
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{{Structure
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|PDB= 1n5o |SIZE=350|CAPTION= <scene name='initialview01'>1n5o</scene>, resolution 2.80&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene> and <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene>
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|ACTIVITY=
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|GENE= BRCA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''Structural consequences of a cancer-causing BRCA1-BRCT missense mutation'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1N5O is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CO:'>CO</scene> and <scene name='pdbligand=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N5O OCA].
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1N5O is a [[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=1N5O OCA].
==Reference==
==Reference==
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Structural consequences of a cancer-causing BRCA1-BRCT missense mutation., Williams RS, Glover JN, J Biol Chem. 2003 Jan 24;278(4):2630-5. Epub 2002 Nov 8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12427738 12427738]
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Structural consequences of a cancer-causing BRCA1-BRCT missense mutation., Williams RS, Glover JN, J Biol Chem. 2003 Jan 24;278(4):2630-5. Epub 2002 Nov 8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12427738 12427738]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: protein folding]]
[[Category: protein folding]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:02:32 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:52:26 2008''

Revision as of 10:52, 20 March 2008

Image:1n5o.gif


PDB ID 1n5o

Drag the structure with the mouse to rotate
, resolution 2.80Å
Ligands: and
Gene: BRCA1 (Homo sapiens)
Coordinates: save as pdb, mmCIF, xml



Structural consequences of a cancer-causing BRCA1-BRCT missense mutation


Contents

Overview

The integrity of the carboxyl-terminal BRCT repeat region is critical for BRCA1 tumor suppressor function; however, the molecular details of how a number of clinically derived BRCT missense mutations affect BRCA1 function remain largely unknown. Here we assess the structural response of the BRCT tandem repeat domain to a well characterized, cancer-associated single amino acid substitution, Met-1775 --> Arg-1775. The structure of BRCT-M1775R reveals that the mutated side chain is extruded from the protein hydrophobic core, thereby altering the protein surface. Charge-charge repulsion, rearrangement of the hydrophobic core, and disruption of the native hydrogen bonding network at the interface between the two BRCT repeats contribute to the conformational instability of BRCT-M1775R. Destabilization and global unfolding of the mutated BRCT domain at physiological temperatures explain the pleiotropic molecular and genetic defects associated with the BRCA1-M1775R protein.

Disease

Known diseases associated with this structure: Breast cancer-1 OMIM:[113705], Breast-ovarian cancer OMIM:[113705], Ovarian cancer OMIM:[113705], Papillary serous carcinoma of the peritoneum OMIM:[113705]

About this Structure

1N5O is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural consequences of a cancer-causing BRCA1-BRCT missense mutation., Williams RS, Glover JN, J Biol Chem. 2003 Jan 24;278(4):2630-5. Epub 2002 Nov 8. PMID:12427738

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