|CATH domain||Related DB codes (homologues)|
|Protein name||Estrogen sulfotransferase, testis isoform||Estrogen sulfotransferase||estrone sulfotransferase3'-phosphoadenylyl sulfate-estrone 3-sulfotransferaseestrogen sulfotransferaseestrogen sulphotransferaseoestrogen sulphotransferase3'-phosphoadenylylsulfate:oestrone sulfotransferase|
|Synonyms||EC 126.96.36.199Sulfotransferase, estrogen-preferring||EC 188.8.131.52Sulfotransferase, estrogen-preferringEST-1|
|MAP00150||Androgen and estrogen metabolism|
|Activity||3''-phosphoadenylyl sulfate + estrone = adenosine 3'',5''-bisphosphate + estrone 3-sulfate.||3''-phosphoadenylyl sulfate + estrone = adenosine 3'',5''-bisphosphate + estrone 3-sulfate.|
|Subunit||Homodimer (By similarity).||Homodimer.|
|Compound||3'-Phosphoadenylylsulfate||Estrone||Adenosine 3',5'-bisphosphate||Estrone 3-sulfate|
|Type||amine group,nucleotide,sulfate group||aromatic ring (only carbon atom),carbohydrate,steroid||amine group,nucleotide||aromatic ring (only carbon atom),carbohydrate,steroid,sulfate group|
|References for Catalytic Mechanism|
|References||Sections||No. of steps in catalysis|
|Journal||Nat Struct Biol|
|Authors||Kakuta Y, Pedersen LG, Carter CW, Negishi M, Pedersen LC|
|Title||Crystal structure of estrogen sulphotransferase.|
|Journal||J Biol Chem|
|Authors||Kakuta Y, Petrotchenko EV, Pedersen LC, Negishi M|
|Title||The sulfuryl transfer mechanism. Crystal structure of a vanadate complex of estrogen sulfotransferase and mutational analysis.|
|Journal||J Biol Chem|
|Authors||Zhang H, Varlamova O, Vargas FM, Falany CN, Leyh TS, Varmalova O|
|Title||Sulfuryl transfer: the catalytic mechanism of human estrogen sulfotransferase.|
|Journal||Arch Biochem Biophys|
|Authors||Negishi M, Pedersen LG, Petrotchenko E, Shevtsov S, Gorokhov A, Kakuta Y, Pedersen LC|
|Title||Structure and function of sulfotransferases.|
|Journal||J Biol Chem|
|Authors||Pedersen LC, Petrotchenko E, Shevtsov S, Negishi M|
|Title||Crystal structure of the human estrogen sulfotransferase-PAPS complex: evidence for catalytic role of Ser137 in the sulfuryl transfer reaction.|
|According to the paper , the catalytic mechanism of this enzyme, EST, can involve SN2 attack by the 3alpha-pehoxide of the substrate on the sulfate of PAPS. Moreover, the trigonal bi-pyramidal transition state intermediate of the reaction could be stablized by positively charged Lys106 and Lys48.|
This paper also mentioned the fundamental differences between sulfonation and phosphorylation . In sulfonation, the charge on the transferred sulfur trioxide [SO3] is 0, whilst the charge on the metaphosphate [PO3-] is -1 for phosphorylation at physiological pH. Moreover, catalysis involving phosphorylation frequently requires presence of a metal ion, usually magnesium. Yet, there is little evidence suggesting that metal ions are required for sulfotransferase activity .
The literature  reported the transition-state like structure with EST-PAP-vanadate complex, in which vanadium atom mimicks the transferring sulfate group. The structure suggested the transition state of an in-line transfer reaction. The stabilization by Lys48, His108, and Lys106 of the transition state may also be essential for the high catalytic efficiency .
According to the literature , the catalytic mechanism is proposed as follows:
The conserved histidine (His108 for 1aqu) can be a general base that abstracts the proton from the acceptor hydroxy group, thereby converting this group to a strong nuceophile. Once formed, the nucleophile attacks the sulfur atom of PAPS, which in turn leads to an accumulation of negative charge at the bridging oxygen (i.e., leaving oxygen) between the 5'-phosphate and sulfate. On the other hand, the conserved lysine (Lys48 for 1aqu) residue may donate its proton to the bridging oxygen, thereby assisting in the dissociation of the sulfate group from PAPS. This catalytic lysine must also stabilize the transient state in aiding the dissociation of the sulfate from the PAPS.
The conserved serine residue (Ser138 for 1aqu) seems to regulate the sulfur transfer reaction as the switch for the catalytic lysine, through its interaction. The sidechain coordination of the serine residue to the catalytic lysine occurs subsequent to the binding of the 3'-phosphate of PAPS to this serine. Whereas the serine interacts with the lysine to decrease the PAPS hydrolysis, the sidechain nitrogen of the lysine must be coordinated with the bridging oxygen to play a role as catalytic acid. The conserved histidine may play the major role in the switch as the catalytic base. Following the substrate binding, the histidine removes the proton from the acceptor group, making it the nucleophile that subsequently attacks the sulfur atom of the PAPS molecule. Negative charge accumulates on the bridging oxygen. Finally, the developing negative charge forces the sidechain nitrogen of the catalytic lysine to switch from the serine to the bridging oxygen and the sulfate dissociation occurs ,.