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Article: Discovery of a natural product inhibitor targeting protein neddylation by structure-based virtual screening

TitleDiscovery of a natural product inhibitor targeting protein neddylation by structure-based virtual screening
Authors
KeywordsDrug Discovery
Natural Product
Nedd8-Activating Enzyme
Ubiquitin-Like Protein
Virtual Screening
Issue Date2012
PublisherElsevier France, Editions Scientifiques et Medicales. The Journal's web site is located at http://www.elsevier.com/locate/biochi
Citation
Biochimie, 2012, v. 94 n. 11, p. 2457-2460 How to Cite?
AbstractNEDD8-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. © 2012 Elsevier Masson SAS. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/168656
ISSN
2015 Impact Factor: 2.474
2015 SCImago Journal Rankings: 1.462
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhong, HJen_US
dc.contributor.authorPuiYan Ma, Ven_US
dc.contributor.authorCheng, Zen_US
dc.contributor.authorShiuHin Chan, Den_US
dc.contributor.authorHe, HZen_US
dc.contributor.authorLeung, KHen_US
dc.contributor.authorMa, DLen_US
dc.contributor.authorLeung, CHen_US
dc.date.accessioned2012-10-08T03:24:03Z-
dc.date.available2012-10-08T03:24:03Z-
dc.date.issued2012en_US
dc.identifier.citationBiochimie, 2012, v. 94 n. 11, p. 2457-2460en_US
dc.identifier.issn0300-9084en_US
dc.identifier.urihttp://hdl.handle.net/10722/168656-
dc.description.abstractNEDD8-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. © 2012 Elsevier Masson SAS. All rights reserved.en_US
dc.languageengen_US
dc.publisherElsevier France, Editions Scientifiques et Medicales. The Journal's web site is located at http://www.elsevier.com/locate/biochien_US
dc.relation.ispartofBiochimieen_US
dc.subjectDrug Discoveryen_US
dc.subjectNatural Producten_US
dc.subjectNedd8-Activating Enzymeen_US
dc.subjectUbiquitin-Like Proteinen_US
dc.subjectVirtual Screeningen_US
dc.titleDiscovery of a natural product inhibitor targeting protein neddylation by structure-based virtual screeningen_US
dc.typeArticleen_US
dc.identifier.emailMa, DL:edmondma@hku.hken_US
dc.identifier.emailLeung, CH:duncanl@hkucc.hku.hken_US
dc.identifier.authorityMa, DL=rp00760en_US
dc.identifier.authorityLeung, CH=rp00730en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.biochi.2012.06.004en_US
dc.identifier.pmid22709868-
dc.identifier.scopuseid_2-s2.0-84867397251en_US
dc.identifier.isiWOS:000310929200028-
dc.publisher.placeFranceen_US
dc.identifier.scopusauthoridZhong, HJ=55068315800en_US
dc.identifier.scopusauthoridPuiYan Ma, V=55276529700en_US
dc.identifier.scopusauthoridCheng, Z=37039284500en_US
dc.identifier.scopusauthoridShiuHin Chan, D=36348783900en_US
dc.identifier.scopusauthoridHe, HZ=35995462000en_US
dc.identifier.scopusauthoridLeung, KH=55066271900en_US
dc.identifier.scopusauthoridMa, DL=7402075538en_US
dc.identifier.scopusauthoridLeung, CH=7402612570en_US
dc.identifier.citeulike11533430-

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