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Structural Insight into the Interactions between Structurally Similar Inhibitors and SIRT6

Sirtuin 6 (SIRT6) is an NAD+-dependent deacetylase with a significant role in 20% of all cancers, such as colon cancers and rectal adenocarcinoma. However, there is currently no effective drug for cancers related to SIRT6. To explore potential inhibitors of SIRT6, it is essential to reveal details o...

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Autores principales: Zhao, Shuang, Zhu, Yan-Yan, Wang, Xiao-Yu, Liu, Yong-Sheng, Sun, Yun-Xiang, Zhao, Qing-Jie, Li, Hui-Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178056/
https://www.ncbi.nlm.nih.gov/pubmed/32283646
http://dx.doi.org/10.3390/ijms21072601
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author Zhao, Shuang
Zhu, Yan-Yan
Wang, Xiao-Yu
Liu, Yong-Sheng
Sun, Yun-Xiang
Zhao, Qing-Jie
Li, Hui-Yu
author_facet Zhao, Shuang
Zhu, Yan-Yan
Wang, Xiao-Yu
Liu, Yong-Sheng
Sun, Yun-Xiang
Zhao, Qing-Jie
Li, Hui-Yu
author_sort Zhao, Shuang
collection PubMed
description Sirtuin 6 (SIRT6) is an NAD+-dependent deacetylase with a significant role in 20% of all cancers, such as colon cancers and rectal adenocarcinoma. However, there is currently no effective drug for cancers related to SIRT6. To explore potential inhibitors of SIRT6, it is essential to reveal details of the interaction mechanisms between inhibitors and SIRT6 at the atomic level. The nature of small molecules from herbs have many advantages as inhibitors. Based on the conformational characteristics of the inhibitor Compound 9 (Asinex ID: BAS13555470), we explored the natural molecule Scutellarin, one compound of Huang Qin, which is an effective herb for curing cancer that has been described in the Traditional Chinese Medicine (TCMS) library. We investigated the interactions between SIRT6 and the inhibitors using molecular dynamics (MD) simulations. We illustrated that the structurally similar inhibitors have a similar binding mode to SIRT6 with residues—Leu9, Phe64, Val115, His133 and Trp188. Hydrophobic and π-stacking interactions play important roles in the interactions between SIRT6 and inhibitors. In summary, our results reveal the interactive mechanism of SIRT6 and the inhibitors and we also provide Scutellarin as a new potential inhibitor of SIRT6. Our study provides a new potential way to explore potential inhibitors from TCMS.
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spelling pubmed-71780562020-04-28 Structural Insight into the Interactions between Structurally Similar Inhibitors and SIRT6 Zhao, Shuang Zhu, Yan-Yan Wang, Xiao-Yu Liu, Yong-Sheng Sun, Yun-Xiang Zhao, Qing-Jie Li, Hui-Yu Int J Mol Sci Article Sirtuin 6 (SIRT6) is an NAD+-dependent deacetylase with a significant role in 20% of all cancers, such as colon cancers and rectal adenocarcinoma. However, there is currently no effective drug for cancers related to SIRT6. To explore potential inhibitors of SIRT6, it is essential to reveal details of the interaction mechanisms between inhibitors and SIRT6 at the atomic level. The nature of small molecules from herbs have many advantages as inhibitors. Based on the conformational characteristics of the inhibitor Compound 9 (Asinex ID: BAS13555470), we explored the natural molecule Scutellarin, one compound of Huang Qin, which is an effective herb for curing cancer that has been described in the Traditional Chinese Medicine (TCMS) library. We investigated the interactions between SIRT6 and the inhibitors using molecular dynamics (MD) simulations. We illustrated that the structurally similar inhibitors have a similar binding mode to SIRT6 with residues—Leu9, Phe64, Val115, His133 and Trp188. Hydrophobic and π-stacking interactions play important roles in the interactions between SIRT6 and inhibitors. In summary, our results reveal the interactive mechanism of SIRT6 and the inhibitors and we also provide Scutellarin as a new potential inhibitor of SIRT6. Our study provides a new potential way to explore potential inhibitors from TCMS. MDPI 2020-04-09 /pmc/articles/PMC7178056/ /pubmed/32283646 http://dx.doi.org/10.3390/ijms21072601 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhao, Shuang
Zhu, Yan-Yan
Wang, Xiao-Yu
Liu, Yong-Sheng
Sun, Yun-Xiang
Zhao, Qing-Jie
Li, Hui-Yu
Structural Insight into the Interactions between Structurally Similar Inhibitors and SIRT6
title Structural Insight into the Interactions between Structurally Similar Inhibitors and SIRT6
title_full Structural Insight into the Interactions between Structurally Similar Inhibitors and SIRT6
title_fullStr Structural Insight into the Interactions between Structurally Similar Inhibitors and SIRT6
title_full_unstemmed Structural Insight into the Interactions between Structurally Similar Inhibitors and SIRT6
title_short Structural Insight into the Interactions between Structurally Similar Inhibitors and SIRT6
title_sort structural insight into the interactions between structurally similar inhibitors and sirt6
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178056/
https://www.ncbi.nlm.nih.gov/pubmed/32283646
http://dx.doi.org/10.3390/ijms21072601
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