Structural Insight into the Interactions between Structurally Similar Inhibitors and SIRT6

doi:10.3390/ijms21072601

	Structural Insight into the Interactions between Structurally Similar Inhibitors and SIRT6
	Zhao, Shuang 2; Zhu, Yan-Yan 2; Wang, Xiao-Yu 2; Liu, Yong-Sheng 2; Sun, Yun-Xiang 1; Zhao, Qing-Jie 3; Li, Hui-Yu 1
刊名	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
	2020-04-01
卷号	21 期号:7 页码:15
关键词	SIRT6 inhibitor nature molecule molecular dynamics simulation scutellarin hydrophobic interactions pi-stacking interactions binding sites
DOI	10.3390/ijms21072601
通讯作者	Zhao, Qing-Jie(zhaoqingjie@simm.ac.cn) ; Li, Hui-Yu(huiyuli@shiep.edu.cn)
英文摘要	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 pi-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.
资助项目	National Natural Science Foundation of China[11674215] ; National Natural Science Foundation of China[51672172]
WOS关键词	SCUTELLARIA-BARBATA ; DEACETYLASE ; EXPRESSION ; FLAVONOIDS ; MECHANISM ; SIRTUINS ; EXTRACT ; FAMILY
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
语种	英语
出版者	MDPI
WOS记录号	WOS:000535574200343
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/280136]
专题	中国科学院上海药物研究所
通讯作者	Zhao, Qing-Jie; Li, Hui-Yu
作者单位	1.Ningbo Univ, Dept Phys, Ningbo 315211, Peoples R China 2.Shanghai Univ Elect Power, Dept Math & Phys, Shanghai 20090, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhao, Shuang,Zhu, Yan-Yan,Wang, Xiao-Yu,et al. Structural Insight into the Interactions between Structurally Similar Inhibitors and SIRT6[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2020,21(7):15.
APA	Zhao, Shuang.,Zhu, Yan-Yan.,Wang, Xiao-Yu.,Liu, Yong-Sheng.,Sun, Yun-Xiang.,...&Li, Hui-Yu.(2020).Structural Insight into the Interactions between Structurally Similar Inhibitors and SIRT6.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,21(7),15.
MLA	Zhao, Shuang,et al."Structural Insight into the Interactions between Structurally Similar Inhibitors and SIRT6".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 21.7(2020):15.