IRMA ERIKA HERAWATI, - and RONNY LESMANA, - and JUTTI LEVITA, - and ANAS SUBARNAS, - (2021) MOLECULAR INTERACTION OF RICIN-A WITH CASPASE-3, CASPASE-8, CASPASE-9 AND AUTOPHAGY-RELATED GENE5 (ATG5) TO UNDERSTAND ITS ROLE AS ANTICANCER AGENT. Rasayan Journal Chemistry, 14 (3). pp. 1790-1794.
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Abstract
The stimulation of caspases, i.e. intracellular cysteine proteases which cleave their substrates at aspartic acid residues, can lead to apoptosis. Autophagy, the regulated cellular degradation, is commenced from the engulfment of unwanted cytoplasmic content, followed by the fusion with the lysosome, and the degradation. Ricin contained in the seeds of Ricinus communis L. is a type II ribosome-inactivating protein that possesses cytotoxicity activity against various cancer cell lines. Our work investigated the structure-based molecular interaction of caspase-3, -8, -9, and autophagyrelated gene5 (ATG5) with ricin-A. The X-ray crystal structures of human caspase-3, -8, -9, and ATG5 were retrieved from https://www.rcsb.org/structure/. The protein-protein docking was performed by employing ClusPro (https://cluspro.org/). The results indicated that ricin-A reveals similar binding modes in terms of the hydrogen bond (Ser205, Arg207, Ser209) and hydrophobic interaction (Trp206 and Phe256) with those of Ac-DEVD-AFC (a caspase3 substrate). Ricin-A interacts with Arg413 and Ser411 that were located antiparallel in the binding pocket of caspase8. A part of ricin-A also binds to Val410, a residue located in pocket S2 of caspase-8. Moreover, ricin-A interacts with several amino acid residues in caspase-9, thus activation of caspase-9 by ricin-A occurs on an allosteric site. Several hydrogen bonds are built between ricin-A and residues 395-479 in ATG5. In conclusion, ricin-A might be able to induce the downstream executioner caspases, particularly caspase-3, -8, -9, and modulates ATG5, thus activates apoptosis and inhibits autophagy.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Apoptosis, Autophagy, Caspase, Ricin-A, Ricinus communis L. |
| Subjects: | Q Science > Q Science (General) R Medicine > R Medicine (General) |
| Divisions: | Lembaga Penelitian dan Pengabdian Masyarakat > Publikasi Penelitian |
| Depositing User: | Irma Erika - - |
| Date Deposited: | 03 Jul 2025 05:13 |
| Last Modified: | 03 Jul 2025 05:13 |
| URI: | http://repository.stfi.ac.id/id/eprint/2579 |
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