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Sulfation through the looking glass—recent advances in sulfotransferase research for the curious

The Pharmacogenomics Journal volume 2, pages 297–308 (2002)Cite this article

Abstract

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.

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Notes

  1. Raftogianis RB et al, submitted for publication. In particular, the new nomenclature for the SULT1C enzymes may cause some confusion. The human SULT1C2 referred to here was called SULT1C1 or SULT1C sulfotransferase 1 in the original descriptions,18,19,75 and the human SULT1C4 referred to here was originally called SULT1C2 or SULT1C sulfotransferase.19,75

  2. This may not be the case for liver, where the presence of other SULT isoforms such as 1B1 may interfere with measurement of enzyme activity with non-selective substrates such as 4-nitrophenol (our unpublished work).

Abbreviations

SULT:

Sulfotransferase

PAPS:

3′-phosphoadenosine 5′-phosphosulfate

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Acknowledgements

I am grateful to all the members of my laboratory (past and present), and to numerous valued collaborators, who have contributed to the work and ideas described here. I am particularly indebted to Dr Rebecca Raftogianis (Fox Chase Cancer Center, Philadelphia, USA) for her critical reading of the manuscript and for helpful suggestions regarding nomenclature, and to Professor Jyrki Taskinen (University of Helsinki, Finland) for producing the model upon which Figure 2 is based. Current research in the laboratory is supported by the Medical Research Council, the Commission of the European Communities (QLG3-CT-2000-00930), Tenovus Scotland, the Scottish Office Chief Scientist Office and the Human Drug Conjugation Consortium.

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    MWH Coughtrie

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Coughtrie, M. Sulfation through the looking glass—recent advances in sulfotransferase research for the curious. Pharmacogenomics J 2, 297–308 (2002). https://doi.org/10.1038/sj.tpj.6500117

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