Does molecular docking reveal alternative chemopreventive mechanism of activation of oxidoreductase by sulforaphane isothiocyanates?
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.
Mazur
Pawel
P
Department of Organic Chemistry, Institute of Chemistry, University of Silesia, 40006, Katowice, Poland.
Magdziarz
Tomasz
T
Bak
Andrzej
A
Chilmonczyk
Zdzislaw
Z
Kasprzycka-Guttman
Teresa
T
Misiewicz-Krzemińska
Irena
I
Skupińska
Katarzyna
K
Polanski
Jaroslaw
J
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
D000970:Antineoplastic Agents; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; D001216:Asparagine; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C016766:sulforaphane