2fb8: Difference between revisions
New page: left|200px<br /> <applet load="2fb8" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fb8, resolution 2.900Å" /> '''Structure of the B... |
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[[Image:2fb8. | [[Image:2fb8.jpg|left|200px]]<br /><applet load="2fb8" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="2fb8, resolution 2.900Å" /> | caption="2fb8, resolution 2.900Å" /> | ||
'''Structure of the B-Raf kinase domain bound to SB-590885'''<br /> | '''Structure of the B-Raf kinase domain bound to SB-590885'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
2FB8 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 215 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http:// | 2FB8 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=215:'>215</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FB8 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: kinase domain]] | [[Category: kinase domain]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:24:57 2008'' | ||
Revision as of 18:24, 15 February 2008
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Structure of the B-Raf kinase domain bound to SB-590885
OverviewOverview
Oncogenic BRAF alleles are both necessary and sufficient for cellular, transformation, suggesting that chemical inhibition of the activated, mutant protein kinase may reverse the tumor phenotype. Here, we report the, characterization of SB-590885, a novel triarylimidazole that selectively, inhibits Raf kinases with more potency towards B-Raf than c-Raf., Crystallographic analysis revealed that SB-590885 stabilizes the oncogenic, B-Raf kinase domain in an active configuration, which is distinct from the, previously reported mechanism of action of the multi-kinase inhibitor, BAY43-9006. Malignant cells expressing oncogenic B-Raf show selective, inhibition of mitogen-activated protein kinase activation, proliferation, transformation, and tumorigenicity when exposed to SB-590885, whereas, other cancer cell lines and normal cells display variable sensitivities or, resistance to similar treatment. These studies support the validation of, oncogenic B-Raf as a target for cancer therapy and provide the first, evidence of a correlation between the expression of oncogenic BRAF alleles, and a positive response to a selective B-Raf inhibitor.
DiseaseDisease
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 StructureAbout this Structure
2FB8 is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
ReferenceReference
Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF by the kinase inhibitor SB-590885., King AJ, Patrick DR, Batorsky RS, Ho ML, Do HT, Zhang SY, Kumar R, Rusnak DW, Takle AK, Wilson DM, Hugger E, Wang L, Karreth F, Lougheed JC, Lee J, Chau D, Stout TJ, May EW, Rominger CM, Schaber MD, Luo L, Lakdawala AS, Adams JL, Contractor RG, Smalley KS, Herlyn M, Morrissey MM, Tuveson DA, Huang PS, Cancer Res. 2006 Dec 1;66(23):11100-5. PMID:17145850
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