Caspase-3 Regulatory Mechanisms: Difference between revisions
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== Caspase-3 Active Site and Loop Bundle Analysis== | == Caspase-3 Active Site and Loop Bundle Analysis== | ||
=== Importance of Loop Orientation=== | === Importance of Loop Orientation=== | ||
<StructureSection load=' | <StructureSection load='2H5I' size='500' side='right' caption='Structure of Caspase-3 (PDB entry [[2H5I]])' scene=''> | ||
<scene name='Caspase-3_Regulatory_Mechanisms/ | <scene name='Caspase-3_Regulatory_Mechanisms/Dimer/1'>Caspase-3 Dimer</scene> | ||
Caspases are extremely dependent on the orientation and geometry of their active site loops. If the loops are not ordered properly the enzyme fails to function. Caspase-3 has four active site loops on each half of the dimer constituting the active site bundle. Proteolytic activity is dependent on cleavage of an intersubunit linker, which releases loop 2 (L2) and L2’. <scene name='Caspase-3_Regulatory_Mechanisms/Scene2_nospin_labels/1'>L2'(green spheres) interacts with the opposite half of the dimer by holding up L2 (blue spheres) </scene>. This allows L2 to make critical contacts with L3 and L4, allowing them to organize the active site, bind substrate, and orient the nucleophilic cysteine 163 (bright green) so that it can cleave after aspartate residues. | Caspases are extremely dependent on the orientation and geometry of their active site loops. If the loops are not ordered properly the enzyme fails to function. Caspase-3 has four active site loops on each half of the dimer constituting the active site bundle. Proteolytic activity is dependent on cleavage of an intersubunit linker, which releases loop 2 (L2) and L2’. <scene name='Caspase-3_Regulatory_Mechanisms/Scene2_nospin_labels/1'>L2'(green spheres) interacts with the opposite half of the dimer by holding up L2 (blue spheres) </scene>. This allows L2 to make critical contacts with L3 and L4, allowing them to organize the active site, bind substrate, and orient the nucleophilic cysteine 163 (bright green) so that it can cleave after aspartate residues. |