SULFOTRANSFERASE MOLECULAR-BIOLOGY - CDNAS AND GENES

Sulfotransferase (ST) enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These r eactions result hi enhanced renal excretion of the sulfate-conjugated reaction products, but they call also lead to the formation of ''bioac tivated'' metabolites. ST enzymes are members of an emerging gene supe rfamily that presently includes phenol ST (PST), hydroxysteroid ST (HS ST), and, in plants, flavonol ST (FST) ''families,'' members of which share at least 45% amino acid sequence identity. These families can be further subdivided into ''subfamilies'' that are at least 60% identic al in amino acid sequence. For example, the PST family includes both P ST and estrogen ST (EST) subfamilies. Amino acid sequence motifs exist within ST enzymes that are conserved throughout phylogeny. These sign ature sequences may be involved in the binding of 3'-phosphoadenosine- 5'-phosphosulfate, the cosubstrate for the sulfonation reaction. There are presently five known human cytosolic ST enzymes: an EST, an HSST, and three PSTs. cDNAs and genes for all of these enzymes have been cl oned, and chromosomal localizations have been reported for all five ge nes. Genes for these human enzymes, as well as those of other mammalia n cytosolic ST enzymes that have been cloned, show a high degree of st ructural homology, with conservation of the locations of most intron/e xon splice junctions. Human ST enzyme expression varies among individu als. Functionally significant genetic polymorphisms for ST enzymes in humans have been reported, and other molecular genetic mechanisms that might be involved in the regulation of the expression of these enzyme s are being explored. Knowledge of the molecular biology of cytosolic ST enzymes, when placed within a context provided by decades of bioche mical research, promises to significantly enhance our understanding of the regulation of the sulfate conjugation of hormones, neurotransmitt ers, and drugs.