title: Does molecular docking reveal alternative chemopreventive mechanism of activation of oxidoreductase by sulforaphane isothiocyanates?
abstract: Isothiocyanates (ITC) are well-known chemopreventive agents extracted from vegetables. This activity results from the activation of human oxidoreductase. In this letter, the uncompetitive activatory mechanism of ITC was investigated using docking and molecular dynamics simulations. This indicates that NAD(P)H:quinone oxidoreductase can efficiently improve enzyme-substrate recognition within the catalytic site if the ITC activator supports the interaction in the uncompetitive binding site.
authors.affiliation: Department of Organic Chemistry, Institute of Chemistry, University of Silesia, 40006, Katowice, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Mazur
authors.forename: Tomasz
authors.initials: T
authors.lastname: Magdziarz
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bak
authors.forename: Zdzislaw
authors.initials: Z
authors.lastname: Chilmonczyk
authors.forename: Teresa
authors.initials: T
authors.lastname: Kasprzycka-Guttman
authors.forename: Irena
authors.initials: I
authors.lastname: Misiewicz-Krzemińska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Skupińska
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Polanski
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001216:Asparagine / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D004789:Enzyme Activation; D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity; D013454:Sulfoxides; D013861:Thiocyanates / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; D001216:Asparagine; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C016766:sulforaphane