1uwh
From Proteopedia
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| - | [[Image:1uwh.gif|left|200px]]<br /><applet load="1uwh" size=" | + | [[Image:1uwh.gif|left|200px]]<br /><applet load="1uwh" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1uwh, resolution 2.95Å" /> | caption="1uwh, resolution 2.95Å" /> | ||
'''THE COMPLEX OF WILD TYPE B-RAF AND BAY439006'''<br /> | '''THE COMPLEX OF WILD TYPE B-RAF AND BAY439006'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1UWH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CL and BAX as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Site: <scene name='pdbsite=AC1:Cl Binding Site For Chain B'>AC1</scene>. Full crystallographic information is available from [http:// | + | 1UWH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CL:'>CL</scene> and <scene name='pdbligand=BAX:'>BAX</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Site: <scene name='pdbsite=AC1:Cl+Binding+Site+For+Chain+B'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UWH OCA]. |
==Reference== | ==Reference== | ||
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[[Category: kinase]] | [[Category: kinase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:08:40 2008'' |
Revision as of 08:08, 3 February 2008
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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 with and as ligands. Active as Transferred entry: 2.7.11.1, with EC number 2.7.1.37 Known structural/functional Site: . 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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