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2uzi

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[[Image:2uzi.gif|left|200px]]
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{{Seed}}
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[[Image:2uzi.png|left|200px]]
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{{STRUCTURE_2uzi| PDB=2uzi | SCENE= }}
{{STRUCTURE_2uzi| PDB=2uzi | SCENE= }}
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'''CRYSTAL STRUCTURE OF HRAS(G12V)- ANTI-RAS FV COMPLEX'''
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===CRYSTAL STRUCTURE OF HRAS(G12V)- ANTI-RAS FV COMPLEX===
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==Overview==
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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.
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The line below this paragraph, {{ABSTRACT_PUBMED_17568777}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 17568777 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17568777}}
==About this Structure==
==About this Structure==
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[[Category: Signal transduction]]
[[Category: Signal transduction]]
[[Category: Signaling protein/immune system]]
[[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 Jul 28 07:01:38 2008''

Revision as of 04:01, 28 July 2008

Image:2uzi.png

Template:STRUCTURE 2uzi

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

Template:ABSTRACT PUBMED 17568777

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 Mon Jul 28 07:01:38 2008

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