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 17980	37998 37998	36259 36259	17985 17985		17864 17864
PubChem	10214 10214	115245 115245	439763 439763	159296 159296	443113 443113	440071 440071

1efhA	Unbound	Unbound	Unbound	Bound:A3P	Unbound	Unbound
1efhB	Unbound	Unbound	Unbound	Bound:A3P	Unbound	Unbound
1j99A	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	LYS 44;HIS 99;SER 129
1efhB	LYS 44;HIS 99;SER 129
1j99A	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].

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