Sandbox Reserved 707: Difference between revisions

<scene name='Sandbox_Reserved_707/Cr3_domain/2'>CR3</scene> is the protein kinase domain on the C-terminal region. We can find just after this kinase domain a stimulatory 14-3-3 binding site for other regulatory proteins.<br />

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> 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 />

A <scene name='Sandbox_Reserved_707/Gatekeeper_residue/1'>gatekeeper residue</scene> separates the adenine binding site from the hydrophobic pocket. Mutation on this residue can prevent the binding of kinase inhibitory drugs (the replacement of a threonine by a methionine for example).<br />

It is very important to distinguish conserved amino acid residue signatures that constitute the catalytic core of the B-RAF Kinase. The catalytic properties are done by the <scene name='Sandbox_Reserved_707/Kdd_motif/1'>KDD (Lys578-Asp576-Asp594)</scene> Motif and the <scene name='Sandbox_Reserved_707/Activation_segment/1'>activation segment</scene> starts in general with a <scene name='Sandbox_Reserved_707/Dfg_start_activation_segment/1'>DFG</scene> and ends with <scene name='Sandbox_Reserved_707/Ape/1'>APE</scene>. But how the catalytic reaction is generated?