1n5o
From Proteopedia
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| - | [[Image:1n5o.gif|left|200px]] | + | [[Image:1n5o.gif|left|200px]] |
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| - | '''Structural consequences of a cancer-causing BRCA1-BRCT missense mutation''' | + | {{Structure |
| + | |PDB= 1n5o |SIZE=350|CAPTION= <scene name='initialview01'>1n5o</scene>, resolution 2.80Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene> and <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= BRCA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Structural consequences of a cancer-causing BRCA1-BRCT missense mutation''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1N5O is a [ | + | 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== | ||
| - | 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:// | + | 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]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''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
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| , 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
Page seeded by OCA on Thu Mar 20 12:52:26 2008
Categories: Homo sapiens | Single protein | Glover, J N.M. | Williams, R S. | CO | SO4 | Brca1 | Brct | Breast cancer | Missense mutation | Protein folding
