Sandbox Reserved 707: Difference between revisions
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This cascade participates in the regulation of several cellular mechanisms like: apoptosis, cell cycle progression, differentiation, proliferation and transformation to the cancerous state in response to growth factors, cytokines and hormones. First discovered in 1938<ref>PMID:16649144</ref> as a retroviral oncogene B-RAF plays a key role on all studies concerning cancer therapies and other biomedical applications. | This cascade participates in the regulation of several cellular mechanisms like: apoptosis, cell cycle progression, differentiation, proliferation and transformation to the cancerous state in response to growth factors, cytokines and hormones. First discovered in 1938<ref>PMID:16649144</ref> as a retroviral oncogene B-RAF plays a key role on all studies concerning cancer therapies and other biomedical applications. | ||
== B-RAF Structure<ref>PMID: 15035987</ref> == | == B-RAF Structure<ref>PMID: 15035987</ref> == | ||
<Structure load='1UWH' size='400' frame='true' align='left' caption='3D View of the complex ; resolution 2,95 A' scene='Insert optional scene name here' /> | |||
As we distinguished before, there are 3 types of RAF proteins: A-RAF, B-RAF and C-RAF. All of them share 3 much conserved regions (CR): CR1, CR2 and <scene name='Sandbox_Reserved_707/Cr3_domain/2'>CR3</scene><ref>PMID:15520807</ref>. We have to say here that in the pdb file 1UWH the protein is already dimerized (as we will say it in the next part), and so we have here '''two''' CR3 domains. <br /> | As we distinguished before, there are 3 types of RAF proteins: A-RAF, B-RAF and C-RAF. All of them share 3 much conserved regions (CR): CR1, CR2 and <scene name='Sandbox_Reserved_707/Cr3_domain/2'>CR3</scene><ref>PMID:15520807</ref>. We have to say here that in the pdb file 1UWH the protein is already dimerized (as we will say it in the next part), and so we have here '''two''' CR3 domains. <br /> | ||
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As all RAF Proteins, B-RAF has the characteristic <scene name='Sandbox_Reserved_707/Small_lobe/1'>small N-terminal lobe</scene> and the <scene name='Sandbox_Reserved_707/Large_lobe/1'>large C-terminal lobe</scene>. | As all RAF Proteins, B-RAF has the characteristic <scene name='Sandbox_Reserved_707/Small_lobe/1'>small N-terminal lobe</scene> and the <scene name='Sandbox_Reserved_707/Large_lobe/1'>large C-terminal lobe</scene>. | ||
The small lobe is constituted of an antiparallel β-shift that anchors and orient the ATP. It contains a glycine rich ATP phosphate binding loop, called <scene name='Sandbox_Reserved_707/Glycine_rich_loop/1'>P-loop</scene>. The large lobe interacts with the substrate that in our case is MEK1/2 who needs to be phosphorylated to be active. The <scene name='Sandbox_Reserved_707/Active_site_of_1uwh/1'>catalytic site</scene><ref>PMID:3291115</ref> is just between the two lobes. These 2 lobes can move relative to each other, opening or closing the cleft. This has 2 major consequences on the functioning of this enzyme:<br /> | The small lobe is constituted of an antiparallel β-shift that anchors and orient the ATP. It contains a glycine rich ATP phosphate binding loop, called <scene name='Sandbox_Reserved_707/Glycine_rich_loop/1'>P-loop</scene>. The large lobe interacts with the substrate that in our case is MEK1/2 who needs to be phosphorylated to be active. The <scene name='Sandbox_Reserved_707/Active_site_of_1uwh/1'>catalytic site</scene><ref>PMID:3291115</ref> is just between the two lobes. These 2 lobes can move relative to each other, opening or closing the cleft. This has 2 major consequences on the functioning of this enzyme:<br /> | ||
'''1.''' The open form allows access of ATP and release of ADP from the active site.<br /> | '''1.''' The open form allows access of ATP and release of ADP from the active site.<br /> | ||
'''2.''' The closed form brings the residues of the substrate into the active site.<br /> | '''2.''' The closed form brings the residues of the substrate into the active site.<br /> | ||
