Abstract
The aim of this study was to investigate the chemical space and interactions of natural compounds with sulfotransferases (SULTs) using ligand- and structure-based in silico methods. An in-house library of natural ligands (hormones, neurotransmitters, plant-derived compounds and their metabolites) reported to interact with SULTs was created. Their chemical structures and properties were compared to those of compounds of non-natural (synthetic) origin, known to interact with SULTs. The natural ligands interacting with SULTs were further compared to other natural products for which interactions with SULTs were not known. Various descriptors of the molecular structures were calculated and analyzed. Statistical methods (ANOVA, PCA, and clustering) were used to explore the chemical space of the studied compounds. Similarity search between the compounds in the different groups was performed with the ROCS software. The interactions with SULTs were additionally analyzed by docking into different experimental and modeled conformations of SULT1A1. Natural products with potentially strong interactions with SULTs were outlined. Our results contribute to a better understanding of chemical space and interactions of natural compounds with SULT enzymes and help to outline new potential ligands of these enzymes.
Highlights
Drug-metabolizing enzymes are involved in the metabolism of endogenous molecules and the elimination of xenobiotics and drugs [1,2,3,4]
Natural SULT ligands
Results in the Groups of Compounds clusters were ligands distributed among the clusters with The the ranges other natural products, suggesting similarity, the ligands were of the best docking scores for structural each compound in thebut
Summary
Drug-metabolizing enzymes are involved in the metabolism of endogenous molecules and the elimination of xenobiotics and drugs [1,2,3,4]. Cytosolic sulfotransferases (SULTs) participate in Phase II reactions in the body [6] by catalyzing the sulfuryl group transfer from the co-factor 30 -phosphoadenosine 50 -phosphosulfate (PAPS). To a substrate hydroxyl or amino group of endogenous/exogenous compounds [7,8,9,10]. Some substrates inhibit SULTs and dead-end complexes with bound inactive co-factor PAP can be created. The cytosolic SULTs include 13 enzymes that can be found in many tissues [11]. SULTs metabolize a wide variety of substrates, including endogenous compounds like steroids and polysaccharides, natural compounds [12,13]
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