Sandox Bay Serrano
From Proteopedia
(Difference between revisions)
| Line 3: | Line 3: | ||
Caspases are '''c'''ysteine-'''asp'''artic acid prote'''ases''' and are key protein facilitators for the faithful execution of apoptosis or programmed cell death. Dysregulation in the apoptotic pathway has been implicated in a variety of diseases such as neurodegeneration, cancer, heart disease and some metabolic disorders. Because of the crucial role of caspases in the the apoptotic pathway, abnormalities in their functions would cause a haywire in the apoptotic cascade and can be deleterious to the cell. Caspases are thus being considered as therapeutic targets in apoptosis-related diseases. | Caspases are '''c'''ysteine-'''asp'''artic acid prote'''ases''' and are key protein facilitators for the faithful execution of apoptosis or programmed cell death. Dysregulation in the apoptotic pathway has been implicated in a variety of diseases such as neurodegeneration, cancer, heart disease and some metabolic disorders. Because of the crucial role of caspases in the the apoptotic pathway, abnormalities in their functions would cause a haywire in the apoptotic cascade and can be deleterious to the cell. Caspases are thus being considered as therapeutic targets in apoptosis-related diseases. | ||
| - | + | Any apoptotic signal received by the cell causes the activation of initiator caspases (-8 and -9) by associating with another proteinplatform to form a functional holoenzyme. These initiator caspases then cleaves the executioner caspases -3, -6, -7. Caspase-3 specifically functions to cleave both caspase-6 and -7, which in turn cleave their respective targets to induce cell death. | |
| - | |||
| - | |||
| - | |||
| - | |||
| - | </StructureSection> | ||
<StructureSection load='2h5i_mm1-1.pdb' size='350' side='right' caption='Caspase-3 dimer (PDB entry [[2h5i]])' scene='Sandox_Bay_Serrano/Scene01_dimer/1'> | <StructureSection load='2h5i_mm1-1.pdb' size='350' side='right' caption='Caspase-3 dimer (PDB entry [[2h5i]])' scene='Sandox_Bay_Serrano/Scene01_dimer/1'> | ||
'''Caspase-3 Structure''' | '''Caspase-3 Structure''' | ||
| - | Caspases are synthesized in the cell in their zymogen form, consisting of an N-terminal prodomain followed by a <scene name='Sandox_Bay_Serrano/Dimer_gray/1'>large and small subunit</scene> linked to each other by an intersubunit linker. As an executioner caspase, caspase-3 has a short N-terminal prodomain and like any other caspases, cleavage of the intersubunit linker at a specific aspartate residue generates the mature form of the enzyme, consisting of the . Caspase-3 in its functional form is dimeric, with the dimer interface being stabilized by interactions between the small subunits of each monomer. Binding of a <scene name='Sandox_Bay_Serrano/Scene01_substrate/2'>substrate</scene>, such as DEVD-CHO to the active site of the enzyme induces a conformational change that allows the L2 and L2' loops to interlock and stabilize the active site <scene name='Sandox_Bay_Serrano/Scene01_substrate/3'></scene>. | + | Caspases are synthesized in the cell in their zymogen form, consisting of an N-terminal prodomain followed by a <scene name='Sandox_Bay_Serrano/Dimer_gray/1'>large and small subunit</scene> linked to each other by an intersubunit linker. As an executioner caspase, caspase-3 has a short N-terminal prodomain and like any other caspases, cleavage of the intersubunit linker at a specific aspartate residue generates the mature form of the enzyme, consisting of the large and small subunits. Caspase-3 in its functional form is dimeric, with the dimer interface being stabilized by interactions between the small subunits of each monomer. Binding of a <scene name='Sandox_Bay_Serrano/Scene01_substrate/2'>substrate</scene>, such as DEVD-CHO to the active site of the enzyme induces a conformational change that allows the L2 and L2' loops to interlock and stabilize the active site <scene name='Sandox_Bay_Serrano/Scene01_substrate/3'></scene>. |
Revision as of 20:04, 12 December 2012
Introduction
Caspases are cysteine-aspartic acid proteases and are key protein facilitators for the faithful execution of apoptosis or programmed cell death. Dysregulation in the apoptotic pathway has been implicated in a variety of diseases such as neurodegeneration, cancer, heart disease and some metabolic disorders. Because of the crucial role of caspases in the the apoptotic pathway, abnormalities in their functions would cause a haywire in the apoptotic cascade and can be deleterious to the cell. Caspases are thus being considered as therapeutic targets in apoptosis-related diseases.
Any apoptotic signal received by the cell causes the activation of initiator caspases (-8 and -9) by associating with another proteinplatform to form a functional holoenzyme. These initiator caspases then cleaves the executioner caspases -3, -6, -7. Caspase-3 specifically functions to cleave both caspase-6 and -7, which in turn cleave their respective targets to induce cell death.
| |||||||||||
