Sulfation through the looking glass--recent advances in sulfotransferase research for the curious.
Members of the cytosolic sulfotransferase (SULT) superfamily catalyse the sulfation of a multitude of xenobiotics, hormones and neurotransmitters. Humans have at least 10 functional SULT genes, and a number of recent advances reviewed here have furthered our understanding of SULT function. Analysis of expression patterns has shown that sulfotransferases are highly expressed in the fetus, and SULTs may in fact be a major detoxification enzyme system in the developing human. The X-ray crystal structures of three SULTs have been solved and combined with mutagenesis experiments and molecular modelling, they have provided the first clues as to the factors that govern the unique substrate specificities of some of these enzymes. In the future these and other studies will facilitate prediction of the fate of chemicals metabolised by sulfation. Variation in sulfation capacity may be important in determining an individual's response to xenobiotics, and there has been an explosion in information on sulfotransferase polymorphisms and their functional consequences, including the influence of SULT1A1 genotype on susceptibility to colorectal and breast cancer. Finally, the first gene knockout experiments with SULTs have recently been described, with the generation of estrogen sulfotransferase deficient mice in which reproductive capacity is compromised. Our improved understanding of these enzymes will have significant benefits in such diverse areas as drug design and development, cancer susceptibility, reproduction and development.
Coughtrie
M W H
MW
Department of Molecular & Cellular Pathology, University of Dundee, Ninewells Hospital & Medical School, Dundee, Scotland, UK. m.w.h.coughtrie@dundee.ac.uk
D000818:Animals; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods / Q000639:trends*; D015238:Sulfotransferases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D013678:Technology, Pharmaceutical / Q000379:methods / Q000639:trends*
D015238:Sulfotransferases