2j20: Difference between revisions

Revision as of 08:14, 4 May 2008

HUMAN P53 CORE DOMAIN MUTANT M133L-V203A-N239Y-N268D-R273C

OverviewOverview

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.

About this StructureAbout this Structure

2J20 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Sun May 4 08:14:01 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:2j20.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2j20 |SIZE=350|CAPTION= <scene name='initialview01'>2j20</scene>, resolution 1.8&Aring;
+The line below this paragraph, containing "STRUCTURE_2j20", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+B'>AC1</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY=
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_2j20|  PDB=2j20  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2j20 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j20 OCA], [http://www.ebi.ac.uk/pdbsum/2j20 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2j20 RCSB]</span>
-}}
 '''HUMAN P53 CORE DOMAIN MUTANT M133L-V203A-N239Y-N268D-R273C'''
@@ Line 28: / Line 25: @@
 [[Category: Fersht, A R.]]
 [[Category: Joerger, A C.]]
-[[Category: acetylation]]
+[[Category: Acetylation]]
-[[Category: activator]]
+[[Category: Activator]]
-[[Category: alternative splicing]]
+[[Category: Alternative splicing]]
-[[Category: anti-oncogene]]
+[[Category: Anti-oncogene]]
-[[Category: apoptosis]]
+[[Category: Apoptosis]]
-[[Category: cell cycle]]
+[[Category: Cell cycle]]
-[[Category: disease mutation]]
+[[Category: Disease mutation]]
-[[Category: dna-binding]]
+[[Category: Dna-binding]]
-[[Category: dna-binding protein]]
+[[Category: Dna-binding protein]]
-[[Category: glycoprotein]]
+[[Category: Glycoprotein]]
-[[Category: host-virus interaction]]
+[[Category: Host-virus interaction]]
-[[Category: li-fraumeni syndrome]]
+[[Category: Li-fraumeni syndrome]]
-[[Category: metal-binding]]
+[[Category: Metal-binding]]
-[[Category: nuclear protein]]
+[[Category: Nuclear protein]]
-[[Category: p53 dna-binding domain]]
+[[Category: P53 dna-binding domain]]
-[[Category: phosphorylation]]
+[[Category: Phosphorylation]]
-[[Category: polymorphism]]
+[[Category: Polymorphism]]
-[[Category: second-site suppressor mutation]]
+[[Category: Second-site suppressor mutation]]
-[[Category: superstable mutant]]
+[[Category: Superstable mutant]]
-[[Category: transcription]]
+[[Category: Transcription]]
-[[Category: transcription regulation]]
+[[Category: Transcription regulation]]
-[[Category: transferase]]
+[[Category: Transferase]]
-[[Category: tumor suppressor]]
+[[Category: Tumor suppressor]]
-[[Category: zinc]]
+[[Category: Zinc]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 08:14:01 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:51:59 2008''