DB code: S00310

RLCP classification 3.203.800.83 : Transfer
CATH domain 3.40.50.300 : Rossmann fold Catalytic domain
E.C. 2.8.2.4
CSA 1hy3
M-CSA 1hy3
MACiE M0154

CATH domain Related DB codes (homologues)
3.40.50.300 : Rossmann fold S00527 S00547 S00548 S00550 S00554 S00555 S00671 S00672 S00676 S00680 S00682 S00913 S00914 S00301 S00302 S00303 S00304 S00307 S00308 S00305 S00306 S00309 S00311 M00114 M00199 D00129 D00130 D00540 M00186

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam RefSeq
P49891 Estrogen sulfotransferase, testis isoform
EC 2.8.2.4
Sulfotransferase, estrogen-preferring
PF00685 (Sulfotransfer_1)
[Graphical View]
P49888 Estrogen sulfotransferase
EC 2.8.2.4
Sulfotransferase, estrogen-preferring
EST-1
PF00685 (Sulfotransfer_1)
[Graphical View]
NP_005411.1 (Protein)
NM_005420.2 (DNA/RNA sequence)

KEGG enzyme name
estrone sulfotransferase
3'-phosphoadenylyl sulfate-estrone 3-sulfotransferase
estrogen sulfotransferase
estrogen sulphotransferase
oestrogen sulphotransferase
3'-phosphoadenylylsulfate:oestrone sulfotransferase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P49891 ST1E1_MOUSE 3''-phosphoadenylyl sulfate + estrone = adenosine 3'',5''-bisphosphate + estrone 3-sulfate. Homodimer (By similarity). Cytoplasm.
P49888 ST1E1_HUMAN 3''-phosphoadenylyl sulfate + estrone = adenosine 3'',5''-bisphosphate + estrone 3-sulfate. Homodimer. Cytoplasm.

KEGG Pathways
Map code Pathways E.C.
MAP00150 Androgen and estrogen metabolism
MAP00920 Sulfur metabolism

Compound table
Substrates Products Intermediates
KEGG-id C00053 C00468 C00054 C02538
E.C.
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
ChEBI 17980
17263
17985
17474
PubChem 10214
5870
159296
3001028
1aquA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:EST Bound:A3P Unbound Unbound
1aquB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:EST Bound:A3P Unbound Unbound
1aqyA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:A3P Unbound Unbound
1aqyB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:A3P Unbound Unbound
1bo6A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:A3P Unbound Transtion-state-analogue:A3P-VO4
1bo6B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:A3P Unbound Transtion-state-analogue:A3P-VO4
1hy3A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:PPS Unbound Unbound Unbound Unbound
1hy3B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:PPS Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [1],[4]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1aquA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 48;LYS 106;HIS 108;SER 138
1aquB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 48;LYS 106;HIS 108;SER 138
1aqyA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 48;LYS 106;HIS 108;SER 138
1aqyB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 48;LYS 106;HIS 108;SER 138
1bo6A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 48;LYS 106;HIS 108;SER 138
1bo6B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 48;LYS 106;HIS 108;SER 138
1hy3A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 47;LYS 105;HIS 107;SER 137
1hy3B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 47;LYS 105;HIS 107;SER 137

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.906-907
[2]
Fig.4, p.27327-27329 2
[4]
Fig.4, p.152-154 2
[5]
Fig.5, p.17931 2

References
[1]
Resource
Comments
Medline ID
PubMed ID 9360604
Journal Nat Struct Biol
Year 1997
Volume 4
Pages 904-8
Authors Kakuta Y, Pedersen LG, Carter CW, Negishi M, Pedersen LC
Title Crystal structure of estrogen sulphotransferase.
Related PDB 1aqu 1aqy 1bo6
Related UniProtKB P49891
[2]
Resource
Comments
Medline ID
PubMed ID 9765259
Journal J Biol Chem
Year 1998
Volume 273
Pages 27325-30
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.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 9556564
Journal J Biol Chem
Year 1998
Volume 273
Pages 10888-92
Authors Zhang H, Varlamova O, Vargas FM, Falany CN, Leyh TS, Varmalova O
Title Sulfuryl transfer: the catalytic mechanism of human estrogen sulfotransferase.
Related PDB
Related UniProtKB
[4]
Resource
Comments Review
Medline ID
PubMed ID
Journal Arch Biochem Biophys
Year 2001
Volume 390
Pages 149-57
Authors Negishi M, Pedersen LG, Petrotchenko E, Shevtsov S, Gorokhov A, Kakuta Y, Pedersen LC
Title Structure and function of sulfotransferases.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 11884392
Journal J Biol Chem
Year 2002
Volume 277
Pages 17928-32
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.
Related PDB 1hy3
Related UniProtKB

Comments
According to the paper [1], 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 [1]. 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 [1].
The literature [2] 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 [2].
According to the literature [4], 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 [4],[5].

Created Updated
2002-05-02 2009-02-26