EzCatDB: S00310

DB codeS00310
RLCP classification3.203.800.83
CATH domainDomain 13.40.50.300Catalytic domain
E.C.2.8.2.4
CSA1hy3
MACiEM0154

CATH domainRelated DB codes (homologues)
3.40.50.300S00527,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

Enzyme Name
Swiss-protKEGG

P49891P49888
Protein nameEstrogen sulfotransferase, testis isoformEstrogen sulfotransferaseestrone sulfotransferase
3'-phosphoadenylyl sulfate-estrone 3-sulfotransferase
estrogen sulfotransferase
estrogen sulphotransferase
oestrogen sulphotransferase
3'-phosphoadenylylsulfate:oestrone sulfotransferase
SynonymsEC 2.8.2.4
Sulfotransferase, estrogen-preferring
EC 2.8.2.4
Sulfotransferase, estrogen-preferring
EST-1

KEGG pathways
MAP codePathways
MAP00150Androgen and estrogen metabolism
MAP00920Sulfur metabolism

Swiss-prot:Accession NumberP49891P49888
Entry nameST1E1_MOUSEST1E1_HUMAN
Activity3''-phosphoadenylyl sulfate + estrone = adenosine 3'',5''-bisphosphate + estrone 3-sulfate.3''-phosphoadenylyl sulfate + estrone = adenosine 3'',5''-bisphosphate + estrone 3-sulfate.
SubunitHomodimer (By similarity).Homodimer.
Subcellular locationCytoplasm.Cytoplasm.
Cofactor



SubstratesProductsintermediates
KEGG-idC00053C00468C00054C02538
Compound3'-PhosphoadenylylsulfateEstroneAdenosine 3',5'-bisphosphateEstrone 3-sulfate
Typeamine group,nucleotide,sulfate grouparomatic ring (only carbon atom),carbohydrate,steroidamine group,nucleotidearomatic ring (only carbon atom),carbohydrate,steroid,sulfate group
1aquAUnboundAnalogue:ESTBound:A3PUnboundUnbound
1aquBUnboundAnalogue:ESTBound:A3PUnboundUnbound
1aqyAUnboundUnboundBound:A3PUnboundUnbound
1aqyBUnboundUnboundBound:A3PUnboundUnbound
1bo6AUnboundUnboundBound:A3PUnboundTranstion-state-analogue:A3P-VO4
1bo6BUnboundUnboundBound:A3PUnboundTranstion-state-analogue:A3P-VO4
1hy3ABound:PPSUnboundUnboundUnboundUnbound
1hy3BBound:PPSUnboundUnboundUnboundUnbound

Active-site residues
resource
literature [1],[4]
pdbCatalytic residues
1aquALYS 48;LYS 106;HIS 108;SER 138
1aquBLYS 48;LYS 106;HIS 108;SER 138
1aqyALYS 48;LYS 106;HIS 108;SER 138
1aqyBLYS 48;LYS 106;HIS 108;SER 138
1bo6ALYS 48;LYS 106;HIS 108;SER 138
1bo6BLYS 48;LYS 106;HIS 108;SER 138
1hy3ALYS 47;LYS 105;HIS 107;SER 137
1hy3BLYS 47;LYS 105;HIS 107;SER 137

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.906-907
[2]Fig.4, p.27327-273292
[4]Fig.4, p.152-1542
[5]Fig.5, p.179312

references
[1]
PubMed ID9360604
JournalNat Struct Biol
Year1997
Volume4
Pages904-8
AuthorsKakuta Y, Pedersen LG, Carter CW, Negishi M, Pedersen LC
TitleCrystal structure of estrogen sulphotransferase.
Related PDB1aqu,1aqy,1bo6
Related Swiss-protP49891
[2]
PubMed ID9765259
JournalJ Biol Chem
Year1998
Volume273
Pages27325-30
AuthorsKakuta Y, Petrotchenko EV, Pedersen LC, Negishi M
TitleThe sulfuryl transfer mechanism. Crystal structure of a vanadate complex of estrogen sulfotransferase and mutational analysis.
[3]
PubMed ID9556564
JournalJ Biol Chem
Year1998
Volume273
Pages10888-92
AuthorsZhang H, Varlamova O, Vargas FM, Falany CN, Leyh TS, Varmalova O
TitleSulfuryl transfer: the catalytic mechanism of human estrogen sulfotransferase.
[4]
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.
[5]
PubMed ID11884392
JournalJ Biol Chem
Year2002
Volume277
Pages17928-32
AuthorsPedersen LC, Petrotchenko E, Shevtsov S, Negishi M
TitleCrystal structure of the human estrogen sulfotransferase-PAPS complex: evidence for catalytic role of Ser137 in the sulfuryl transfer reaction.
Related PDB1hy3

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].

createdupdated
2002-05-022009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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