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Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates
Published on: February 27, 2016
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Structural Insight into the Interactions between Structurally Similar Inhibitors and SIRT6
Shuang Zhao1, Yan-Yan Zhu1, Xiao-Yu Wang1
1Department of Mathematics and Physics, Shanghai University of Electric Power, Shanghai 20090, China.
International Journal of Molecular Sciences
|April 15, 2020
Summary
Scutellarin, a natural compound, shows potential as a Sirtuin 6 (SIRT6) inhibitor for cancer treatment. Molecular dynamics simulations revealed its binding mechanism, offering a new avenue for drug discovery from Traditional Chinese Medicine.
Area of Science:
- Biochemistry and Molecular Biology
- Pharmacology
- Computational Chemistry
Background:
- Sirtuin 6 (SIRT6) is implicated in various cancers, including colon and rectal adenocarcinoma, yet effective drugs are lacking.
- Understanding atomic-level interactions between SIRT6 and inhibitors is crucial for developing targeted therapies.
- Natural products offer a promising source for identifying novel anticancer agents.
Purpose of the Study:
- To investigate the potential of Scutellarin, a natural compound from Traditional Chinese Medicine (TCM), as a Sirtuin 6 (SIRT6) inhibitor.
- To elucidate the molecular interactions between SIRT6 and structurally similar inhibitors at the atomic level.
- To explore the utility of Traditional Chinese Medicine (TCM) resources for discovering novel cancer therapeutics.
Main Methods:
- Molecular dynamics (MD) simulations were employed to study the interactions between SIRT6 and potential inhibitors.
- Conformational analysis of Compound 9 (Asinex ID: BAS13555470) guided the selection of Scutellarin.
- Binding modes and key interacting residues were identified through simulation analysis.
Main Results:
- Scutellarin demonstrated a similar binding mode to SIRT6 as other inhibitors, interacting with key residues like Leu9, Phe64, Val115, His133, and Trp188.
- Hydrophobic and π-stacking interactions were identified as critical for the binding of inhibitors to SIRT6.
- The study identified Scutellarin as a novel potential inhibitor of SIRT6, highlighting its therapeutic promise.
Conclusions:
- The study reveals the interactive mechanism between SIRT6 and its inhibitors at an atomic level.
- Scutellarin is proposed as a new potential inhibitor for Sirtuin 6 (SIRT6)-related cancers.
- This research provides a novel strategy for identifying potential anticancer drugs from Traditional Chinese Medicine (TCM) resources.
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