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Discovery of a natural product inhibitor targeting protein neddylation by structure-based virtual screening
Zhong H.-J.1,2; Pui-Yan Ma V.3; Cheng Z.3; Shiu-Hin Chan D.3; He H.-Z.3; Leung K.-H.3; Ma D.-L.3; Leung C.-H.1,2
2012
Source PublicationBiochimie
ISSN3009084
Volume94Issue:11Pages:2457-2460
Abstract

NEDD8-activating enzyme (NAE) controls the specific degradation of proteins regulated by cullin-RING ubiquitin E3 ligase, and has been considered as an attractive molecular target for the development of anti-cancer drugs. We report herein the identification of the dipeptide-conjugated deoxyvasicinone derivative (1) as an inhibitor of NAE by virtual screening of over 90,000 compounds from the ZINC database of natural products. Molecular modelling results suggested that 1 may be a non-covalent competitive inhibitor of NAE by blocking the ATP-binding domain. Compound 1 was able to inhibit NAE activity in both cell-free and cell-based assay with potencies in the micromolar range and selectivity over analogous E1 enzymes UAE and SAE. We envisage that the identification and molecular docking analysis of this bioactive scaffold as an NAE inhibitor would provide the scientific community with useful information in order to generate more potent analogues.

KeywordDrug Discovery Natural Product Nedd8-activating Enzyme Ubiquitin-like Protein Virtual Screening
DOI10.1016/j.biochi.2012.06.004
URLView the original
Indexed BySCIE
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000310929200028
The Source to ArticleScopus
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Cited Times [WOS]:43   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorMa D.-L.; Leung C.-H.
Affiliation1.Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China
2.State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao SAR, China
3.Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong
First Author AffilicationInstitute of Chinese Medical Sciences;  University of Macau
Corresponding Author AffilicationInstitute of Chinese Medical Sciences;  University of Macau
Recommended Citation
GB/T 7714
Zhong H.-J.,Pui-Yan Ma V.,Cheng Z.,et al. Discovery of a natural product inhibitor targeting protein neddylation by structure-based virtual screening[J]. Biochimie,2012,94(11):2457-2460.
APA Zhong H.-J..,Pui-Yan Ma V..,Cheng Z..,Shiu-Hin Chan D..,He H.-Z..,...&Leung C.-H..(2012).Discovery of a natural product inhibitor targeting protein neddylation by structure-based virtual screening.Biochimie,94(11),2457-2460.
MLA Zhong H.-J.,et al."Discovery of a natural product inhibitor targeting protein neddylation by structure-based virtual screening".Biochimie 94.11(2012):2457-2460.
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