1tsr
From Proteopedia
(New page: 200px<br /> <applet load="1tsr" size="450" color="white" frame="true" align="right" spinBox="true" caption="1tsr, resolution 2.200Å" /> '''P53 CORE DOMAIN IN...) |
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| - | [[Image:1tsr.gif|left|200px]]<br /> | + | [[Image:1tsr.gif|left|200px]]<br /><applet load="1tsr" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1tsr" size=" | + | |
caption="1tsr, resolution 2.200Å" /> | caption="1tsr, resolution 2.200Å" /> | ||
'''P53 CORE DOMAIN IN COMPLEX WITH DNA'''<br /> | '''P53 CORE DOMAIN IN COMPLEX WITH DNA'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Mutations in the p53 tumor suppressor are the most frequently observed | + | Mutations in the p53 tumor suppressor are the most frequently observed genetic alterations in human cancer. The majority of the mutations occur in the core domain which contains the sequence-specific DNA binding activity of the p53 protein (residues 102-292), and they result in loss of DNA binding. The crystal structure of a complex containing the core domain of human p53 and a DNA binding site has been determined at 2.2 angstroms resolution and refined to a crystallographic R factor of 20.5 percent. The core domain structure consists of a beta sandwich that serves as a scaffold for two large loops and a loop-sheet-helix motif. The two loops, which are held together in part by a tetrahedrally coordinated zinc atom, and the loop-sheet-helix motif form the DNA binding surface of p53. Residues from the loop-sheet-helix motif interact in the major groove of the DNA, while an arginine from one of the two large loops interacts in the minor groove. The loops and the loop-sheet-helix motif consist of the conserved regions of the core domain and contain the majority of the p53 mutations identified in tumors. The structure supports the hypothesis that DNA binding is critical for the biological activity of p53, and provides a framework for understanding how mutations inactivate it. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1TSR 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 ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1TSR 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=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TSR OCA]. |
==Reference== | ==Reference== | ||
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[[Category: tumor suppressor]] | [[Category: tumor suppressor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:16:54 2008'' |
Revision as of 13:16, 21 February 2008
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P53 CORE DOMAIN IN COMPLEX WITH DNA
Contents |
Overview
Mutations in the p53 tumor suppressor are the most frequently observed genetic alterations in human cancer. The majority of the mutations occur in the core domain which contains the sequence-specific DNA binding activity of the p53 protein (residues 102-292), and they result in loss of DNA binding. The crystal structure of a complex containing the core domain of human p53 and a DNA binding site has been determined at 2.2 angstroms resolution and refined to a crystallographic R factor of 20.5 percent. The core domain structure consists of a beta sandwich that serves as a scaffold for two large loops and a loop-sheet-helix motif. The two loops, which are held together in part by a tetrahedrally coordinated zinc atom, and the loop-sheet-helix motif form the DNA binding surface of p53. Residues from the loop-sheet-helix motif interact in the major groove of the DNA, while an arginine from one of the two large loops interacts in the minor groove. The loops and the loop-sheet-helix motif consist of the conserved regions of the core domain and contain the majority of the p53 mutations identified in tumors. The structure supports the hypothesis that DNA binding is critical for the biological activity of p53, and provides a framework for understanding how mutations inactivate it.
Disease
Known diseases associated with this structure: Adrenal cortical carcinoma OMIM:[191170], Breast cancer OMIM:[191170], Colorectal cancer OMIM:[191170], Hepatocellular carcinoma OMIM:[191170], Histiocytoma OMIM:[191170], Li-Fraumeni syndrome OMIM:[191170], Multiple malignancy syndrome OMIM:[191170], Nasopharyngeal carcinoma OMIM:[191170], Osteosarcoma OMIM:[191170], Pancreatic cancer OMIM:[191170], Thyroid carcinoma OMIM:[191170]
About this Structure
1TSR is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations., Cho Y, Gorina S, Jeffrey PD, Pavletich NP, Science. 1994 Jul 15;265(5170):346-55. PMID:8023157
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