DB code: S00309

RLCP classification 3.203.800.83 : Transfer
CATH domain 3.40.50.300 : Rossmann fold Catalytic domain
E.C. 2.8.2.14
CSA
M-CSA
MACiE

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 S00310 S00311 M00114 M00199 D00129 D00130 D00540 M00186

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q06520 Bile salt sulfotransferase
EC 2.8.2.14
Hydroxysteroid Sulfotransferase
HST
Dehydroepiandrosterone sulfotransferase
DHEA-ST
ST2
ST2A3
NP_003158.2 (Protein)
NM_003167.3 (DNA/RNA sequence)
PF00685 (Sulfotransfer_1)
[Graphical View]

KEGG enzyme name
bile-salt sulfotransferase
BAST I
bile acid:3'-phosphoadenosine-5'-phosphosulfate sulfotransferase
bile salt:3'phosphoadenosine-5'-phosphosulfate:sulfotransferase
bile acid sulfotransferase I
glycolithocholate sulfotransferase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q06520 ST2A1_HUMAN 3''-phosphoadenylyl sulfate + glycolithocholate = adenosine 3'',5''-bisphosphate + glycolithocholate 3-sulfate. 3''-phosphoadenylyl sulfate + taurolithocholate = adenosine 3'',5''-bisphosphate + taurolithocholate sulfate. Homodimer. Cytoplasm.

KEGG Pathways
Map code Pathways E.C.

Compound table
Substrates Products Intermediates
KEGG-id C00053 C15557 C02592 C00054 C11301 C03642
E.C.
Compound 3'-Phosphoadenylylsulfate Glycolithocholate Taurolithocholate Adenosine 3',5'-bisphosphate Sulfoglycolithocholate Taurolithocholate sulfate
Type amine group,nucleotide ,sulfate group amide group,carbohydrate,carboxyl group,steroid amide group,carbohydrate,steroid,sulfonate group amine group,nucleotide amide group,carboxyl group,steroid,sulfate group amide group,steroid,sulfonate group,sulfate group
ChEBI 17980
37998
36259
17985
17864
PubChem 10214
115245
439763
159296
443113
440071
1efhA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:A3P Unbound Unbound
1efhB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Bound:A3P Unbound Unbound
1j99A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:AND Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [3]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1efhA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 44;HIS 99;SER 129
1efhB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 44;HIS 99;SER 129
1j99A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain LYS 44;HIS 99;SER 129

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
p.62
[3]
Fig.4, p.152-154 2

References
[1]
Resource
Comments
Medline ID
PubMed ID 9584614
Journal Trends Biochem Sci
Year 1998
Volume 23
Pages 129-30
Authors Kakuta Y, Pedersen LG, Pedersen LC, Negishi M
Title Conserved structural motifs in the sulfotransferase family.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 10854859
Journal FEBS Lett
Year 2000
Volume 475
Pages 61-4
Authors Pedersen LC, Petrotchenko EV, Negishi M
Title Crystal structure of SULT2A3, human hydroxysteroid sulfotransferase.
Related PDB 1efh
Related UniProtKB
[3]
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

Comments
According to the literature [3], the catalytic mechanism is proposed as follows:
(1) The conserved histidine (His99) can be a general base that abstracts the proton from the acceptor hydroxy group, thereby converting this group to a strong nuceophile.
(2) The activated hydroxyl oxygen makes a nucleophilic attacks on 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.
(3) On the other hand, the conserved lysine (Lys44) residue may act as a general acid to donate its proton to the bridging oxygen (as a stabilizer), 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.
(3') The conserved serine residue (Ser129) seems to regulate the sulfur transfer reaction as the switch for the catalytic lysine, through its interaction. The sidechain coordination of the serine residue (Ser129) to the catalytic lysine occurs subsequently 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.
(4) The histidine residue (His99) acts as a general acid to protonate the transferred sulfuryl group.
Taken together, the conserved histidine (His99) 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 [3].

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