Caspase-3 Regulatory Mechanisms
From Proteopedia
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== Regulation of Caspase-3== | == Regulation of Caspase-3== | ||
| - | ===Exosite and Allosteric Site=== | + | === Exosite and Allosteric Site=== |
Caspases have similar structure of active site. Exosite that could be utilized to improve activity has been found in caspase-7 (Boucher, Blais et al. 2012). Caspase-7 also has an inhibitory allosteric site that could bind with small molecule FICA, presenting a zymogen-like conformation (Hardy, Lam et al. 2004). | Caspases have similar structure of active site. Exosite that could be utilized to improve activity has been found in caspase-7 (Boucher, Blais et al. 2012). Caspase-7 also has an inhibitory allosteric site that could bind with small molecule FICA, presenting a zymogen-like conformation (Hardy, Lam et al. 2004). | ||
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| - | ====Post translational Modification==== | + | ==== Post translational Modification==== |
| - | ====Natural Inhibitors==== | + | ==== Natural Inhibitors==== |
X-linked inhibitor of apoptosis proteins (XIAP) contains the second baculovirus IAP repeat domain (BIR2) targeting caspase-3 and caspase-7. | X-linked inhibitor of apoptosis proteins (XIAP) contains the second baculovirus IAP repeat domain (BIR2) targeting caspase-3 and caspase-7. | ||
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| - | Reference | + | =Reference= |
Bose, K., C. Pop, et al. (2003). "An uncleavable procaspase-3 mutant has a lower catalytic efficiency but an active site similar to that of mature caspase-3." Biochemistry 42(42): 12298-12310. | Bose, K., C. Pop, et al. (2003). "An uncleavable procaspase-3 mutant has a lower catalytic efficiency but an active site similar to that of mature caspase-3." Biochemistry 42(42): 12298-12310. | ||
Revision as of 18:23, 12 December 2012
Introduction
Caspases are cysteine-dependent aspartic acid proteases and are the key facilitators of apoptosis or programmed cell death. Apoptosis is tightly regulated by these caspases, and dysregulation of caspase functions have been implicated in wide variety of diseases such as neurodegeneration, cancer, heart disease and some metabolic disorders. As such, caspases are considered to be attractive drug targets to treat these disorders.
Existing as proenzymes, caspases undergo proteolytic processing at conserved aspartate residues in their intersubunit linker to produce the large and small subunit. These subunits then dimerize to form the active enzyme. Any apoptotic signal received by the cell results in sequential activation of caspases. Upstream or initator caspases (-2,-8, -9 and -10) are first activated by forming a holoenzyme wherein they associate with another protein platform or adaptor protein. Once active, initiator caspases cleave and activate the executioner caspases (-3, -6 and -7) which in turn cleave their respective protein targets initiating cell death.
Caspase-3 structure
Caspase-3 Active Site and Loop Bundle Analysis
Lets give it a shot.
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Proteopedia Page Contributors and Editors (what is this?)
Scott Eron, Banyuhay P. Serrano, Alexander Berchansky, Yunlong Zhao, Jaime Prilusky, Michal Harel
