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1n5o
From Proteopedia
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|PDB= 1n5o |SIZE=350|CAPTION= <scene name='initialview01'>1n5o</scene>, resolution 2.80Å | |PDB= 1n5o |SIZE=350|CAPTION= <scene name='initialview01'>1n5o</scene>, resolution 2.80Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene> | + | |LIGAND= <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= BRCA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= BRCA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1jnx|1JNX]] | ||
| + | |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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==Disease== | ==Disease== | ||
| - | Known | + | Known disease associated with this structure: Breast cancer-1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=113705 113705]], Breast-ovarian cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=113705 113705]], Ovarian cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=113705 113705]], Papillary serous carcinoma of the peritoneum OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=113705 113705]] |
==About this Structure== | ==About this Structure== | ||
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[[Category: Glover, J N.M.]] | [[Category: Glover, J N.M.]] | ||
[[Category: Williams, R S.]] | [[Category: Williams, R S.]] | ||
| - | [[Category: CO]] | ||
| - | [[Category: SO4]] | ||
[[Category: brca1]] | [[Category: brca1]] | ||
[[Category: brct]] | [[Category: brct]] | ||
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[[Category: protein folding]] | [[Category: protein folding]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:25:44 2008'' |
Revision as of 19:25, 30 March 2008
| |||||||
| , resolution 2.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | BRCA1 (Homo sapiens) | ||||||
| Related: | 1JNX
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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 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 Sun Mar 30 22:25:44 2008
