1n5o

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[[Image:1n5o.gif|left|200px]]
[[Image:1n5o.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1n5o |SIZE=350|CAPTION= <scene name='initialview01'>1n5o</scene>, resolution 2.80&Aring;
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The line below this paragraph, containing "STRUCTURE_1n5o", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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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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|DOMAIN=
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{{STRUCTURE_1n5o| PDB=1n5o | SCENE= }}
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|RELATEDENTRY=[[1jnx|1JNX]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1n5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n5o OCA], [http://www.ebi.ac.uk/pdbsum/1n5o PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1n5o RCSB]</span>
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'''Structural consequences of a cancer-causing BRCA1-BRCT missense mutation'''
'''Structural consequences of a cancer-causing BRCA1-BRCT missense mutation'''
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[[Category: Glover, J N.M.]]
[[Category: Glover, J N.M.]]
[[Category: Williams, R S.]]
[[Category: Williams, R S.]]
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[[Category: brca1]]
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[[Category: Brca1]]
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[[Category: brct]]
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[[Category: Brct]]
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[[Category: breast cancer]]
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[[Category: Breast cancer]]
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[[Category: missense mutation]]
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[[Category: Missense mutation]]
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[[Category: protein folding]]
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[[Category: Protein folding]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 02:07:29 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:25:44 2008''
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Revision as of 23:07, 2 May 2008

Image:1n5o.gif

Template:STRUCTURE 1n5o

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 disease 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 Page seeded by OCA on Sat May 3 02:07:29 2008

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