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''' | + | {{Structure |
| + | |PDB= 1uwh |SIZE=350|CAPTION= <scene name='initialview01'>1uwh</scene>, resolution 2.95Å | ||
| + | |SITE= <scene name='pdbsite=AC1:Cl+Binding+Site+For+Chain+B'>AC1</scene> | ||
| + | |LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene> and <scene name='pdbligand=BAX:4-{4-[({[4-CHLORO-3-(TRIFLUOROMETHYL)PHENYL]AMINO}CARBONYL)AMINO]PHENOXY}-N-METHYLPYRIDINE-2-CARBOXAMIDE'>BAX</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.11.1 Transferred entry: 2.7.11.1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.37 2.7.1.37] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''THE COMPLEX OF WILD TYPE B-RAF AND BAY439006''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1UWH is a [ | + | 1UWH is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UWH OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15035987 15035987] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: kinase]] | [[Category: kinase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:37:42 2008'' |
Revision as of 12:37, 20 March 2008
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| , resolution 2.95Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | and | ||||||
| Activity: | Transferred entry: 2.7.11.1, with EC number 2.7.1.37 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
THE COMPLEX OF WILD TYPE B-RAF AND BAY439006
Contents |
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.
Disease
Known diseases associated with this structure: Adenocarcinoma of lung, somatic OMIM:[164757], Cardiofaciocutaneous syndrome OMIM:[164757], Colorectal cancer, somatic OMIM:[164757], Melanoma, melignant, somatic OMIM:[164757], Nonsmall cell lung cancer, somatic OMIM:[164757]
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 Thu Mar 20 14:37:42 2008
