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From Proteopedia
| This Sandbox is Reserved from January 19, 2016, through August 31, 2016 for use for Proteopedia Team Projects by the class Chemistry 423 Biochemistry for Chemists taught by Lynmarie K Thompson at University of Massachusetts Amherst, USA. This reservation includes Sandbox Reserved 425 through Sandbox Reserved 439. |
Contents |
Caspase 3- 1rhk
Introduction
online: -what are caspases -the importance of caspases and the involved diseases. -How do caspases work generally. -what is caspase-3 -caspase-3 typical characteristics and general functions.
Caspases are a group of dimeric cysteine proteases that play important roles to control the ultimate steps of apoptosis and innate inflammation; they are also very important in cellular development, homeostasis and in a wide range of diseases such as neurodegeneration, ischemia and cancers. During apoptosis, the upstream initiator caspases, caspases 8 and 9, activate with the downstream executioner caspases, caspases 3, 6 and 7, via zymogen maturation. The activated executioner caspases then cleave upwards of 500 key proteins and DNA, which finally cause the death of cells.[1] Caspases 3 () is one of the downstream executioner caspases which interacts with caspase 8 and 9. It is formed from a 32 kDa zymogen that is cleaved into 17 kDa and 12 kDa subunits. Caspase 3 has many of the typical characteristics which all currently-known caspases also own. For instance, its active site contains acysteine residue, Cys-285() and histidine residue () that stabilize the peptide bond cleavage of a protein sequence to the carboxy-terminal side of an aspartic acid when it is part of a particular 4-amino acid sequence.[2] Besides apoptosis, caspase 3 also has many biological functions, such as normal brain development and several significant diseases including Alzheimer’s disease, Polycystic Kidney Disease and Cancers.
For green scenes with teh Cys and His try showing the sidechain and leaving them both on to see if they are close. Prof T
Overall Structure
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-Highlight each of the Three Chains
-Polarity of each of the chains/structures
-Locations of secondary structures
-Affects of the third 5-Length Chain
-Show structure, and location of different inhibitors
Binding Interactions
-Focus on difficulties in finding good inhibitors
-Chemical and conformational changes applied to various inhibitors
-How successful each of the inhibitors used was in the study
-Good drug candidates for inhibition
Binding sites for .
Additional Features
-Role in apoptosis
--How it is activated (green scene of activation ligand?) --catalytic site (if binding interactions doesn't cover this)
-Potential role in stem-cell differentiation:
"rather than by simply limiting self-renewal. In this model, caspase-3 may simultaneously engage factors to promote the gene expression profile and resulting phenotypic changes that result in a specific differentiated cell type" (Abdul-Ghani and Megeney 515)
Credits
Introduction - Di Lin
Overall Structure - Austin Virtue
Drug Binding Site - Jill Moore
Additional Features - Alex Way
References
1.Rehabilitation of a Contract Killer: Caspase-3 Directs Stem Cell Differentiation. Mohammad Abdul-Ghani,Lynn A. Megeney [3]
2.Jeanne A. Hardy and James A. Wells, Dissecting an Allosteric Switch in Caspase-7 Using Chemical and Mutational Probes, THE JOURNAL OF BIOLOGICAL CHEMISTRY,VOL. 284, NO. 38, pp. 26063–26069, September 18, 2009.
