2uzi

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[[Image:2uzi.gif|left|200px]]
[[Image:2uzi.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 2uzi |SIZE=350|CAPTION= <scene name='initialview01'>2uzi</scene>, resolution 2.00&Aring;
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The line below this paragraph, containing "STRUCTURE_2uzi", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=AC1:Zn+Binding+Site+For+Chain+R'>AC1</scene>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=GTP:GUANOSINE-5&#39;-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY=
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|GENE=
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|DOMAIN=
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{{STRUCTURE_2uzi| PDB=2uzi | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2uzi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uzi OCA], [http://www.ebi.ac.uk/pdbsum/2uzi PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2uzi RCSB]</span>
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}}
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'''CRYSTAL STRUCTURE OF HRAS(G12V)- ANTI-RAS FV COMPLEX'''
'''CRYSTAL STRUCTURE OF HRAS(G12V)- ANTI-RAS FV COMPLEX'''
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[[Category: Tanaka, T.]]
[[Category: Tanaka, T.]]
[[Category: Williams, R L.]]
[[Category: Williams, R L.]]
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[[Category: antibody]]
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[[Category: Antibody]]
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[[Category: cancer therapy]]
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[[Category: Cancer therapy]]
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[[Category: disease mutation]]
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[[Category: Disease mutation]]
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[[Category: golgi apparatus]]
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[[Category: Golgi apparatus]]
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[[Category: gtp-binding]]
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[[Category: Gtp-binding]]
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[[Category: immunoglobulin domain]]
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[[Category: Immunoglobulin domain]]
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[[Category: intrabody]]
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[[Category: Intrabody]]
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[[Category: lipoprotein]]
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[[Category: Lipoprotein]]
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[[Category: membrane]]
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[[Category: Membrane]]
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[[Category: methylation]]
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[[Category: Methylation]]
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[[Category: nucleotide-binding]]
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[[Category: Nucleotide-binding]]
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[[Category: oncogene]]
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[[Category: Oncogene]]
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[[Category: palmitate]]
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[[Category: Palmitate]]
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[[Category: prenylation]]
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[[Category: Prenylation]]
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[[Category: proto-oncogene]]
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[[Category: Proto-oncogene]]
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[[Category: signal transduction]]
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[[Category: Signal transduction]]
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[[Category: signaling protein/immune system]]
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[[Category: Signaling protein/immune system]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 17:52:49 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:06:40 2008''
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Revision as of 14:52, 4 May 2008

Image:2uzi.gif

Template:STRUCTURE 2uzi

CRYSTAL STRUCTURE OF HRAS(G12V)- ANTI-RAS FV COMPLEX


Overview

Many disease-related processes occur via protein complexes that are considered undruggable with small molecules. An example is RAS, which is frequently mutated in cancer and contributes to initiation and maintenance of the disease by constitutive signal transduction through protein interaction with effector proteins, like PI3K, RAF and RALGDS. Such protein interactions are therefore significant targets for therapy. We describe a single immunoglobulin variable region domain that specifically binds to activated GTP-bound RAS and prevents RAS-dependent tumorigenesis in a mouse model. The crystal structure of the immunoglobulin-RAS complex shows that the variable region competitively binds to the conformationally variant regions of RAS, where its signalling effector molecules interact. This allows the plasma membrane targeted single domain intrabody to inhibit signalling by mutant RAS. This mode of action is a novel advance to directly interfere with oncogenic RAS function in human cancer and shows a universally applicable approach to develop macromolecules to combat cancer. In addition, this method illustrates a general means for interfering with protein interactions that are commonly considered intractable as conventional drug targets.

About this Structure

2UZI is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Tumour prevention by a single antibody domain targeting the interaction of signal transduction proteins with RAS., Tanaka T, Williams RL, Rabbitts TH, EMBO J. 2007 Jul 11;26(13):3250-9. Epub 2007 Jun 14. PMID:17568777 Page seeded by OCA on Sun May 4 17:52:49 2008

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OCA

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