Sulfotransferases (SULTs)

 Sulfotransferases can be either membrane-bound in the Golgi or in the cytosol.

While the membrane-bound SULTs sulfonate large molecules such as

glucosaminylglycans, the cytosolic enzymes are involved in the inactivation of

endogenous signal molecules (steroids, thyroid hormones, neurotransmitters) and the

biotransformation ofxenobiotics.

 Each cytosolic SULT is a single a/p globular protein with a characteristic five-

stranded parallel sheet, with a-helices flanking each sheet. The active enzyme is a

homodimer, with each polypeptide chain having a MW of about 35,000. Kakuta et al.

(1997) were the first group to solve the first X-ray structure for the SULT family. Mouse

estrogen sulfotransferase (mEST) was shown completed with PAP and the substrate

estradiol (E2). The binding of estradiol to human SULTIAl has also been demonstrated

(Gamage et al., 2005). Both PAPS- and substrate-binding sites are located deep in the

hydrophobic substrate pocket. The structures of four human cytosolic enzymes have also

been elucidated : SULT 1Al (Gamage et al., 2003), dop ami ne/c atechol ami ne

sulfotransferase (SULTIA3) (Bidwell et al., 1999; Dajani et al., 1999), hydroxysteroid

sulfotransferase (SULT2Al; hHST) (Pedersen et al., 2000), and estrogen sulfotransferase

(SULTIE1; hEST) (Pedersen et al., 2002).

 Five SULT gene families have been identified in mammals (SULTsl-5). While

SULT enzymes have different substrate specificities, the repertoire of suitable substrates

is so broad that it is not uncommon that one substrate is biotransformed by more than one

enzyme. SULTs are distributed in a wide variety of tissues (Table 2-2). In humans, liver

cytosol has been shown to contain mostly SULTslA1, 2A1, and 1E1, with lesser amounts