Sulfotransferase molecular biology: cDNAs and genes

Abstract

Sulfotransferase (ST) enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These reactions result in enhanced renal excretion of the sulfate-conjugated reaction products, but they can also lead to the formation of "bioactivated" metabolites. ST enzymes are members of an emerging gene superfamily that presently includes phenol ST (PST), hydroxysteroid ST (HSST), 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% identical in amino acid sequence. For example, the PST family includes both PST and estrogen ST (EST) subfamilies. Amino acid sequence motifs exist within ST enzymes that are conserved throughout phylogeny. These signature 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 cloned, and chromosomal localizations have been reported for all five genes. Genes for these human enzymes, as well as those of other mammalian cytosolic ST enzymes that have been cloned, show a high degree of structural homology, with conservation of the locations of most intron/exon splice junctions. Human ST enzyme expression varies among individuals. 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 enzymes are being explored. Knowledge of the molecular biology of cytosolic ST enzymes, when placed within a context provided by decades of biochemical research, promises to significantly enhance our understanding of the regulation of the sulfate conjugation of hormones, neurotransmitters, and drugs.

Human cytosolic sulfotransferase database mining: identification of seven novel genes and pseudogenes

“…3 Specifically, the expected lengths of exons, the locations of splice junctions within the predicted cDNA, and the presence of GT/AG dinucleotides flanking exons were considered when annotating exons. Each hit corresponding to a SULT exon was refined using the GCG local sequence alignment program Gap.…”

“…Cytosolic SULTs are usually active as homodimers and share two highly conserved regions of the amino-acid sequence, termed Regions I and IV. 1,3 These regions of sequence are important in binding the cosubstrate sulfate donor molecule 3 0 -phosphoadenosine 5 0 -phosphosulfate (PAPS). [4][5][6] In addition, Region IV forms part of the dimerization interface region for these enzymes.…”

“…7 SULTs can be classified into families whose members share at least 45% amino-acid sequence identity, and subfamilies that include enzymes that share at least 60% amino-acid sequence identity. 3,8 It should be noted that the membrane-bound sulfotransferases which are located in the golgi and catalyze the sulfation of macromolecules form a superfamily distinct from that of the cytosolic SULTs, 9 and were not included in the present study.…”

“…3,[10][11][12][13][14][15] While the cDNAs for some of those genes were cloned after purification and sequencing of the expressed protein, many were subsequently identified and cloned using homology-based techniques that took advantage of the highly conserved sequences in Regions I and IV. Eight of the human genes were characterized using PCR and DNA sequencing methods, 12,[16][17][18][19][20][21] but the genes for SULT1B1 and 4A1 were characterized by annotation of publicly available genomic sequence data generated by the Human Genome Project (unpublished observations 22 ).…”

Molecular cloning, expression, localisation and functional characterisation of a rabbit SULT1C2 sulfotransferase

“…The sulfonation reaction is catalysed by an emerging supergene family of enzymes termed sulfotransferases, with 3′-phosphoadenosine-5′-phosphosulfate (PAPS) acting as the sulfuryl donor [2]. Prior to 1997, more than 30 different forms of cytosolic sulfotransferases (ST) had been characterised from organisms ranging from microbes to humans [3]. Interrogation of ST sequences submitted to GenBank now show that this number has now risen to well over 50.…”