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1uwh
From Proteopedia
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[[Image:1uwh.gif|left|200px]] | [[Image:1uwh.gif|left|200px]] | ||
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'''THE COMPLEX OF WILD TYPE B-RAF AND BAY439006''' | '''THE COMPLEX OF WILD TYPE B-RAF AND BAY439006''' | ||
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[[Category: Roe, S M.]] | [[Category: Roe, S M.]] | ||
[[Category: Wan, P T.C.]] | [[Category: Wan, P T.C.]] | ||
| - | [[Category: | + | [[Category: Kinase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 11:46:39 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 08:46, 3 May 2008
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| 1uwh, resolution 2.95Å () | |||||||||
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| Ligands: | , | ||||||||
| Related: | 1uwj | ||||||||
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| Resources: | FirstGlance, OCA, RCSB, PDBsum | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
THE COMPLEX OF WILD TYPE B-RAF AND BAY439006
Overview
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.
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 Page seeded by OCA on Sat May 3 11:46:39 2008
