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Updated: Jul 6, 2026
05:56
Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches
Published on: October 13, 2022
[Substances modifying the activity of caspases]
T Bartl1, P Zádníková, R Jiríkovská
1Veterinární a farmaceutická univerzita Brno, Farmaceutická fakulta, Ustav chemických léciv. tbartl@vfu.cz
Summary
Caspase inhibitors, including stobadine, theophylline, and adenine derivatives, were studied for their effects on programmed cell death (apoptosis). These compounds demonstrated significant caspase 1 inhibition, with one exceeding 80% effectiveness.
Area of Science:
- Biochemistry
- Molecular Biology
- Enzymology
Context:
- Caspases are crucial enzymes regulating programmed cell death (apoptosis).
- Dysregulation of apoptosis is implicated in various diseases, including cancer, autoimmune disorders, neurodegenerative diseases, and AIDS.
- Identifying modulators of caspase activity is vital for understanding and treating these conditions.
Purpose:
- To investigate the inhibitory effects of stobadine, theophylline, and adenine derivatives on caspase 1 activity.
- To assess the potential of these compounds as therapeutic agents by quantifying their impact on apoptosis.
Summary:
- The study examined the influence of stobadine, theophylline, and adenine derivatives on caspase 1, an enzyme central to apoptosis.
- Spectrophotometry was employed to measure the enzyme's activity in the presence of these compounds.
- All tested compounds exhibited inhibitory effects on caspase 1, with one derivative showing over 80% inhibition.
Impact:
- These findings highlight the potential of specific chemical compounds to modulate caspase activity.
- The identified inhibitors could serve as leads for developing novel therapeutic strategies for diseases associated with apoptosis dysregulation.
- Further research into these caspase inhibitors may offer new avenues for treating cancer, neurodegenerative disorders, and other apoptosis-related pathologies.
Related Concept Videos
01:24Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
01:17The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
01:30Apoptosis
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
01:17Phagocytosis of Apoptotic Cells
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.