1uwj: Difference between revisions

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[[Image:1uwj.jpg|left|200px]]
{{Seed}}
[[Image:1uwj.png|left|200px]]


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{{STRUCTURE_1uwj|  PDB=1uwj  |  SCENE=  }}  
{{STRUCTURE_1uwj|  PDB=1uwj  |  SCENE=  }}  


'''THE COMPLEX OF MUTANT V599E B-RAF AND BAY439006'''
===THE COMPLEX OF MUTANT V599E B-RAF AND BAY439006===




==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.
The line below this paragraph, {{ABSTRACT_PUBMED_15035987}}, adds the Publication Abstract to the page
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{{ABSTRACT_PUBMED_15035987}}


==About this Structure==
==About this Structure==
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[[Category: Signal transduction]]
[[Category: Signal transduction]]
[[Category: Threonine-protein kinase]]
[[Category: Threonine-protein kinase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 11:46:52 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 14:47:08 2008''

Revision as of 11:47, 28 July 2008

File:1uwj.png

Template:STRUCTURE 1uwj

THE COMPLEX OF MUTANT V599E B-RAF AND BAY439006

Template:ABSTRACT PUBMED 15035987

About this Structure

1UWJ 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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