EzCatDB: S00309
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DB codeS00309
RLCP classification3.203.800.83 : Transfer
CATH domainDomain 13.40.50.300 : Rossmann foldCatalytic domain
E.C.2.8.2.14

CATH domainRelated DB codes (homologues)
3.40.50.300 : Rossmann foldS00527,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

Enzyme Name
UniProtKBKEGG

Q06520
Protein nameBile salt sulfotransferasebile-salt sulfotransferase
BAST I
bile acid:3'-phosphoadenosine-5'-phosphosulfate sulfotransferase
bile salt:3'phosphoadenosine-5'-phosphosulfate:sulfotransferase
bile acid sulfotransferase I
glycolithocholate sulfotransferase
SynonymsEC 2.8.2.14
Hydroxysteroid Sulfotransferase
HST
Dehydroepiandrosterone sulfotransferase
DHEA-ST
ST2
ST2A3
RefSeqNP_003158.2 (Protein)
NM_003167.3 (DNA/RNA sequence)
PfamPF00685 (Sulfotransfer_1)
[Graphical view]


UniProtKB:Accession NumberQ06520
Entry nameST2A1_HUMAN
Activity3''-phosphoadenylyl sulfate + glycolithocholate = adenosine 3'',5''-bisphosphate + glycolithocholate 3-sulfate.,3''-phosphoadenylyl sulfate + taurolithocholate = adenosine 3'',5''-bisphosphate + taurolithocholate sulfate.
SubunitHomodimer.
Subcellular locationCytoplasm.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProducts
KEGG-idC00053C15557C02592C00054C11301C03642
Compound3'-PhosphoadenylylsulfateGlycolithocholateTaurolithocholateAdenosine 3',5'-bisphosphateSulfoglycolithocholateTaurolithocholate sulfate
Typeamine group,nucleotide,sulfate groupamide group,carbohydrate,carboxyl group,steroidamide group,carbohydrate,steroid,sulfonate groupamine group,nucleotideamide group,carboxyl group,steroid,sulfate groupamide group,steroid,sulfonate group,sulfate group
ChEBI17980
37998
36259
17985

17864
PubChem10214
115245
439763
159296
443113
440071
              
1efhAUnboundUnboundUnboundBound:A3PUnboundUnbound
1efhBUnboundUnboundUnboundBound:A3PUnboundUnbound
1j99AUnboundAnalogue:ANDUnboundUnboundUnboundUnbound

Active-site residues
resource
literature [3]
pdbCatalytic residues
         
1efhALYS 44;HIS 99;SER 129
1efhBLYS 44;HIS 99;SER 129
1j99ALYS 44;HIS 99;SER 129

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]p.62
[3]Fig.4, p.152-1542

references
[1]
PubMed ID9584614
JournalTrends Biochem Sci
Year1998
Volume23
Pages129-30
AuthorsKakuta Y, Pedersen LG, Pedersen LC, Negishi M
TitleConserved structural motifs in the sulfotransferase family.
[2]
PubMed ID10854859
JournalFEBS Lett
Year2000
Volume475
Pages61-4
AuthorsPedersen LC, Petrotchenko EV, Negishi M
TitleCrystal structure of SULT2A3, human hydroxysteroid sulfotransferase.
Related PDB1efh
[3]
CommentsReview
JournalArch Biochem Biophys
Year2001
Volume390
Pages149-57
AuthorsNegishi M, Pedersen LG, Petrotchenko E, Shevtsov S, Gorokhov A, Kakuta Y, Pedersen LC
TitleStructure and function of sulfotransferases.

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].

createdupdated
2002-05-022009-02-26


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