2j1x

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[[Image:2j1x.gif|left|200px]]<br /><applet load="2j1x" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2j1x.gif|left|200px]]
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caption="2j1x, resolution 1.65&Aring;" />
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'''HUMAN P53 CORE DOMAIN MUTANT M133L-V203A-Y220C-N239Y-N268D'''<br />
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{{Structure
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|PDB= 2j1x |SIZE=350|CAPTION= <scene name='initialview01'>2j1x</scene>, resolution 1.65&Aring;
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|SITE= <scene name='pdbsite=AC1:Zn+Binding+Site+For+Chain+B'>AC1</scene>
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|LIGAND= <scene name='pdbligand=ZN:ZINC ION'>ZN</scene>
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|ACTIVITY=
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|GENE=
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}}
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'''HUMAN P53 CORE DOMAIN MUTANT M133L-V203A-Y220C-N239Y-N268D'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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2J1X 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]. Known structural/functional Site: <scene name='pdbsite=AC1:Zn+Binding+Site+For+Chain+B'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J1X OCA].
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2J1X 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=2J1X OCA].
==Reference==
==Reference==
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Structural basis for understanding oncogenic p53 mutations and designing rescue drugs., Joerger AC, Ang HC, Fersht AR, Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15056-61. Epub 2006 Oct 2. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17015838 17015838]
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Structural basis for understanding oncogenic p53 mutations and designing rescue drugs., Joerger AC, Ang HC, Fersht AR, Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15056-61. Epub 2006 Oct 2. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17015838 17015838]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: zinc]]
[[Category: zinc]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:58:33 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:36:20 2008''

Revision as of 15:36, 20 March 2008

Image:2j1x.gif


PDB ID 2j1x

Drag the structure with the mouse to rotate
, resolution 1.65Å
Sites:
Ligands:
Coordinates: save as pdb, mmCIF, xml



HUMAN P53 CORE DOMAIN MUTANT M133L-V203A-Y220C-N239Y-N268D


Contents

Overview

The DNA-binding domain of the tumor suppressor p53 is inactivated by mutation in approximately 50% of human cancers. We have solved high-resolution crystal structures of several oncogenic mutants to investigate the structural basis of inactivation and provide information for designing drugs that may rescue inactivated mutants. We found a variety of structural consequences upon mutation: (i) the removal of an essential contact with DNA, (ii) creation of large, water-accessible crevices or hydrophobic internal cavities with no other structural changes but with a large loss of thermodynamic stability, (iii) distortion of the DNA-binding surface, and (iv) alterations to surfaces not directly involved in DNA binding but involved in domain-domain interactions on binding as a tetramer. These findings explain differences in functional properties and associated phenotypes (e.g., temperature sensitivity). Some mutants have the potential of being rescued by a generic stabilizing drug. In addition, a mutation-induced crevice is a potential target site for a mutant-selective stabilizing drug.

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

2J1X is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural basis for understanding oncogenic p53 mutations and designing rescue drugs., Joerger AC, Ang HC, Fersht AR, Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15056-61. Epub 2006 Oct 2. PMID:17015838

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