1uwh

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[[Image:1uwh.gif|left|200px]]
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{{STRUCTURE_1uwh| PDB=1uwh | SCENE= }}
{{STRUCTURE_1uwh| PDB=1uwh | SCENE= }}
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'''THE COMPLEX OF WILD TYPE B-RAF AND BAY439006'''
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===THE COMPLEX OF WILD TYPE B-RAF AND BAY439006===
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==Overview==
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Over 30 mutations of the B-RAF gene associated with human cancers have been identified, the majority of which are located within the kinase domain. Here we show that of 22 B-RAF mutants analyzed, 18 have elevated kinase activity and signal to ERK in vivo. Surprisingly, three mutants have reduced kinase activity towards MEK in vitro but, by activating C-RAF in vivo, signal to ERK in cells. The structures of wild type and oncogenic V599EB-RAF kinase domains in complex with the RAF inhibitor BAY43-9006 show that the activation segment is held in an inactive conformation by association with the P loop. The clustering of most mutations to these two regions suggests that disruption of this interaction converts B-RAF into its active conformation. The high activity mutants signal to ERK by directly phosphorylating MEK, whereas the impaired activity mutants stimulate MEK by activating endogenous C-RAF, possibly via an allosteric or transphosphorylation mechanism.
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The line below this paragraph, {{ABSTRACT_PUBMED_15035987}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 15035987 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15035987}}
==About this Structure==
==About this Structure==
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[[Category: Wan, P T.C.]]
[[Category: Wan, P T.C.]]
[[Category: Kinase]]
[[Category: Kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 11:46:39 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 12:22:01 2008''

Revision as of 09:22, 28 July 2008

Image:1uwh.png


PDB ID 1uwh

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1uwh, resolution 2.95Å ()
Ligands: ,
Related: 1uwj
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml



THE COMPLEX OF WILD TYPE B-RAF AND BAY439006

Template:ABSTRACT PUBMED 15035987

About this Structure

1UWH is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF., Wan PT, Garnett MJ, Roe SM, Lee S, Niculescu-Duvaz D, Good VM, Jones CM, Marshall CJ, Springer CJ, Barford D, Marais R, Cell. 2004 Mar 19;116(6):855-67. PMID:15035987

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