Introduction: Cytosolic sulfotransferases (SULTs) are the enzymes that catalyze the sulfonation reaction, an important metabolic pathway for numerous endogenous and exogenous compounds. Human SULTs exhibit complex patterns of broad, differential and overlapping substrate selectivity. Moreover, these enzymes often display substrate inhibition kinetics (i.e., inhibition of the enzyme activity at high substrate concentrations).
Areas covered: At present, the crystal structures for 12 human SULTs (i.e., SULT1A1, 1A2, 1A3, 1B1, 1C1, 1C2, 1C3, 1E1, 2A1, 2B1a, 2B1b and 4A1) are available, many of which are in complex with a substrate. This review describes the similarities and differences in these structures (particularly the active-site structures) of SULT enzymes. The authors also discuss the structural basis for understanding the catalytic mechanism, the substrate inhibition mechanisms, the cofactor (3'-phosphoadenosine 5'-phosphosulfate or PAPS) binding and the substrate recognition.
Expert opinion: Correlations of the structural features (including conformational flexibility) in the active sites with the substrate profiles of several SULTs have been well established. One is encouraged to closely integrate in silico approaches with the structural knowledge of the active sites for development of a rationalized and accurate tool that is able to predict metabolism of SULTs toward chemicals and drug candidates.