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Sigma's Non-specific Protease Activity Assay - Casein as a Substrate
Published on: September 17, 2008
Selective Inhibition on RAGE-binding AGEs Required by Bioactive Peptide Alpha-S2 Case in Protein from Goat Ethawah
Fatchiyah Fatchiyah1, Ferlany Hardiyanti1, Nashi Widodo1
1Department of Biology, Faculty of Mathematics and Natural Sciences, University of Brawijaya, Jl Veteran, Malang, 65145, East Java, Indonesia.
Background:
Advanced Glycation End Products (AGE) play a pivotal role in the development various degenerative diseases such as diabetes, cardiovascular disease, stroke, neuropathy, and nephropathy. Different studies have been done to employ AGEs as drug targets for the diseases therapy. In previous study, we have found bioactive peptide from Ethawah goat milk for anti-diabetic that may work through inhibition of AGE receptor function. However, the mechanism of bioactive peptides inhibits AGE- AGE receptor (RAGE) bonding still not clear yet. Therefore we investigated the inhibition mechanism by calculate the potential energy binding among the peptides, AGEs and RAGE using molecular docking system.
Methods:
Modeling 3D-structure was predicted by SWISS-MODEL web server. The virtual interaction was analyzed by docking system using HEX 8.0, Pymol and Discovery Studio 4.0 software.
Results:
this study showed that AGEs (Argypirimidine, Imidazole, Pentosidine and Pyrraline) bind to C-domain of RAGE. The total energy binding of RAGE with Argypirimidine, Imidazole, Pentosidine and Pyrraline were 378.35kJ/mol, -74.57kJ/mol, -301.25kJ/mol and -400.72kJ/mol, respectively. We have found three peptides among eight peptides from Ethawah goat milk, which are able bind to C-domain of RAGE, there are CSN1S2 f41-47, CSN1S2 f182-189, and CSN1S2 f214-221. The CSN1S22 f41-47 at arginine residue 47 interacts with proline162, leusine163 and leusine158 of RAGE. The total binding energy between CSN1S2 f41-47, CSN1S2 f182-189, and CSN1S2 f214-221 with RAGE were -378.35 kJ/mol, -359.97kJ/mol, -356.78 kJ/mol, respectively. Total binding energy and binding pattern indicated that RAGE more prefer bind with peptide and block AGE bind to functional site of RAGE. Further analysis showed that complex peptide-RAGE shifted binding site of AGE on function domain RAGE.
Conclusion:
This study suggested that the peptides from Ethawah goat milk may act as an inhibitor of AGEs-RAGE interaction that impaired signal transduction cascade at the cellular level.
Insights
Bioactive peptides from Ethawah goat milk inhibit the interaction between Advanced Glycation End Products (AGEs) and their receptor (RAGE). This molecular docking study reveals peptides bind to RAGE, blocking AGEs and potentially preventing associated degenerative diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Advanced Glycation End Products (AGEs) are implicated in degenerative diseases like diabetes and cardiovascular conditions.
- Targeting AGEs and their receptor (RAGE) is a therapeutic strategy.
- Previous research identified anti-diabetic peptides in Ethawah goat milk that may inhibit RAGE function.
Purpose of the Study:
- To elucidate the mechanism by which bioactive peptides from Ethawah goat milk inhibit AGE-RAGE binding.
- To analyze the binding energy and interaction patterns using molecular docking.
Main Methods:
- 3D protein structures were modeled using the SWISS-MODEL web server.
- Molecular docking simulations were performed using HEX 8.0, Pymol, and Discovery Studio 4.0.
Main Results:
- AGEs (Argypirimidine, Imidazole, Pentosidine, Pyrraline) bind to the C-domain of RAGE.
- Three Ethawah goat milk peptides (CSN1S2 f41-47, CSN1S2 f182-189, CSN1S2 f214-221) also bind to the RAGE C-domain.
- Peptide-RAGE binding energies ranged from -356.78 to -378.35 kJ/mol, indicating a preference for peptide binding.
- Peptide binding shifts the AGE binding site on RAGE's functional domain.
Conclusions:
- Ethawah goat milk peptides act as inhibitors of AGE-RAGE interactions.
- These peptides may block the AGEs-RAGE signaling cascade at the cellular level.
- This suggests a potential therapeutic role for these peptides in managing AGE-related diseases.
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