Molecular Playground/Executioner Caspase-7: Difference between revisions

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Derek MacPherson, Maureen E. Hill

Revision as of 23:05, 3 December 2013 view source Maureen E. Hill (talk \| contribs) 43 edits No edit summary ← Older edit		Latest revision as of 23:05, 3 December 2013 view source Maureen E. Hill (talk \| contribs) 43 edits No edit summary
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	The <scene name='56/566502/Active_site_conformation/1'>active site</scene> is made up of four flexible loops which include L2, L3 and L4 from one half of the dimer that interact with L2' from the opposite half of the dimer. In the <scene name='56/566502/Procaspase_zymogen/1'>procaspase-7 zymogen</scene>, the loops are disordered, which prevents substrate binding. Upon cleavage at the intersubunit linker, the active-site loop bundle becomes partially ordered, whereas L2' stays in the inactive, down conformation. At this point, caspase-7 may bind either substrate or allosteric inhibitors. <scene name='56/566502/Active_site_substrate_color/1'>Caspase-7 bound to suicide inhibitor/substrate mimc DEVD-CHO</scene> traps the protein an active/substrate bound conformation. Substrate binding forces a conformational change moving L2' upward; this creates a foundation beneath the L2 bundle stabilizing the active complex. Mutagenesis performed within this region of the protein has a significant impact on the ability of the protein to process its substrates. Ultimately, this confirms the importance of L2' stabilizing the active site loop bundle.		The <scene name='56/566502/Active_site_conformation/1'>active site</scene> is made up of four flexible loops which include L2, L3 and L4 from one half of the dimer that interact with L2' from the opposite half of the dimer. In the <scene name='56/566502/Procaspase_zymogen/1'>procaspase-7 zymogen</scene>, the loops are disordered, which prevents substrate binding. Upon cleavage at the intersubunit linker, the active-site loop bundle becomes partially ordered, whereas L2' stays in the inactive, down conformation. At this point, caspase-7 may bind either substrate or allosteric inhibitors. <scene name='56/566502/Active_site_substrate_color/1'>Caspase-7 bound to suicide inhibitor/substrate mimc DEVD-CHO</scene> traps the protein an active/substrate bound conformation. Substrate binding forces a conformational change moving L2' upward; this creates a foundation beneath the L2 bundle stabilizing the active complex. Mutagenesis performed within this region of the protein has a significant impact on the ability of the protein to process its substrates. Ultimately, this confirms the importance of L2' stabilizing the active site loop bundle.


	== Allosteric Inhibition of Caspase-7 ==		== Allosteric Inhibition of Caspase-7 ==