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PDBsum entry 1hy3

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protein ligands Protein-protein interface(s) links
Transferase PDB id
1hy3
Jmol PyMol
Contents
Protein chain
287 a.a. *
Ligands
PPS ×2
Waters ×450
* Residue conservation analysis
PDB id:
1hy3
Name: Transferase
Title: Crystal structure of human estrogen sulfotransferase v269e mutant in the presence of paps
Structure: Estrogen sulfotransferase. Chain: a, b. Synonym: sulfotransferase, estrogen-preferring. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ste. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Resolution:
1.80Å     R-factor:   0.197     R-free:   0.217
Authors: L.C.Pedersen,E.V.Petrochenko,S.Shevtsov,M.Negishi
Key ref:
L.C.Pedersen et al. (2002). Crystal structure of the human estrogen sulfotransferase-PAPS complex: evidence for catalytic role of Ser137 in the sulfuryl transfer reaction. J Biol Chem, 277, 17928-17932. PubMed id: 11884392 DOI: 10.1074/jbc.M111651200
Date:
17-Jan-01     Release date:   19-Jun-02    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P49888  (ST1E1_HUMAN) -  Estrogen sulfotransferase
Seq:
Struc:
294 a.a.
287 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.2.8.2.4  - Estrone sulfotransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 3'-phosphoadenylyl sulfate + estrone = adenosine 3',5'-bisphosphate + estrone 3-sulfate
3'-phosphoadenylyl sulfate
Bound ligand (Het Group name = PPS)
corresponds exactly
+ estrone
= adenosine 3',5'-bisphosphate
+ estrone 3-sulfate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   2 terms 
  Biological process     sulfation   5 terms 
  Biochemical function     protein binding     9 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M111651200 J Biol Chem 277:17928-17932 (2002)
PubMed id: 11884392  
 
 
Crystal structure of the human estrogen sulfotransferase-PAPS complex: evidence for catalytic role of Ser137 in the sulfuryl transfer reaction.
L.C.Pedersen, E.Petrotchenko, S.Shevtsov, M.Negishi.
 
  ABSTRACT  
 
Estrogen sulfotransferase (EST) transfers the sulfate group from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to estrogenic steroids. Here we report the crystal structure of human EST (hEST) in the context of the V269E mutant-PAPS complex, which is the first structure containing the active sulfate donor for any sulfotransferase. Superimposing this structure with the crystal structure of hEST in complex with the donor product 3'-phosphoadenosine 5'-phosphate (PAP) and the acceptor substrate 17beta-estradiol, the ternary structure with the PAPS and estradiol molecule, is modeled. These structures have now provided a more complete view of the S(N)2-like in-line displacement reaction catalyzed by sulfotransferases. In the PAPS-bound structure, the side chain nitrogen of the catalytic Lys(47) interacts with the side chain hydroxyl of Ser(137) and not with the bridging oxygen between the 5'-phosphate and sulfate groups of the PAPS molecule as is seen in the PAP-bound structures. This conformational change of the side chain nitrogen indicates that the interaction of Lys(47) with Ser(137) may regulate PAPS hydrolysis in the absences of an acceptor substrate. Supporting the structural data, the mutations of Ser(137) to cysteine and alanine decrease gradually k(cat) for PAPS hydrolysis and transfer activity. Thus, Ser(137) appears to play an important role in regulating the side chain interaction of Lys(47) with the bridging oxygen between the 5'-phosphate and the sulfate of PAPS.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Superposition of the hEST-PAPS structure with the hEST-PAP-E2 structure. The hydrogen bonding interactions in the PAPS bound structure are represented by black dotted lines, whereas those in the PAP-E2-bound structure are indicated with red dotted lines. Molscript (23) and Raster3D (24) were used to create this figure.
Figure 5.
Fig. 5. Proposed reaction mechanism.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 17928-17932) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20462768 L.M.Danan, Z.Yu, P.J.Ludden, W.Jia, K.L.Moore, and J.A.Leary (2010).
Catalytic mechanism of Golgi-resident human tyrosylprotein sulfotransferase-2: a mass spectrometry approach.
  J Am Soc Mass Spectrom, 21, 1633-1642.  
19250196 J.R.Pasqualini (2009).
Estrogen sulfotransferases in breast and endometrial cancers.
  Ann N Y Acad Sci, 1155, 88-98.  
18928301 E.Tyapochkin, P.F.Cook, and G.Chen (2008).
Isotope exchange at equilibrium indicates a steady state ordered kinetic mechanism for human sulfotransferase.
  Biochemistry, 47, 11894-11899.  
19022906 H.N.Bethea, D.Xu, J.Liu, and L.C.Pedersen (2008).
Redirecting the substrate specificity of heparan sulfate 2-O-sulfotransferase by structurally guided mutagenesis.
  Proc Natl Acad Sci U S A, 105, 18724-18729.
PDB code: 3f5f
18625336 P.Bojarová, and S.J.Williams (2008).
Sulfotransferases, sulfatases and formylglycine-generating enzymes: a sulfation fascination.
  Curr Opin Chem Biol, 12, 573-581.  
17425406 A.Allali-Hassani, P.W.Pan, L.Dombrovski, R.Najmanovich, W.Tempel, A.Dong, P.Loppnau, F.Martin, J.Thornton, J.Thonton, A.M.Edwards, A.Bochkarev, A.N.Plotnikov, M.Vedadi, and C.H.Arrowsmith (2007).
Structural and chemical profiling of the human cytosolic sulfotransferases.
  PLoS Biol, 5, e97.
PDB codes: 1zd1 2ad1 2gwh 2h8k
16801938 M.A.Hildebrandt, D.P.Carrington, B.A.Thomae, B.W.Eckloff, D.J.Schaid, V.C.Yee, R.M.Weinshilboum, and E.D.Wieben (2007).
Genetic diversity and function in the human cytosolic sulfotransferases.
  Pharmacogenomics J, 7, 133-143.  
17110154 N.Hempel, N.Gamage, J.L.Martin, and M.E.McManus (2007).
Human cytosolic sulfotransferase SULT1A1.
  Int J Biochem Cell Biol, 39, 685-689.  
15258569 J.D.Mougous, C.J.Petzold, R.H.Senaratne, D.H.Lee, D.L.Akey, F.L.Lin, S.E.Munchel, M.R.Pratt, L.W.Riley, J.A.Leary, J.M.Berger, and C.R.Bertozzi (2004).
Identification, function and structure of the mycobacterial sulfotransferase that initiates sulfolipid-1 biosynthesis.
  Nat Struct Mol Biol, 11, 721-729.
PDB code: 1tex
15044725 N.Pi, Y.Yu, J.D.Mougous, and J.A.Leary (2004).
Observation of a hybrid random ping-pong mechanism of catalysis for NodST: a mass spectrometry approach.
  Protein Sci, 13, 903-912.  
12922923 A.A.Adjei, B.A.Thomae, J.L.Prondzinski, B.W.Eckloff, E.D.Wieben, and R.M.Weinshilboum (2003).
Human estrogen sulfotransferase (SULT1E1) pharmacogenomics: gene resequencing and functional genomics.
  Br J Pharmacol, 139, 1373-1382.  
  12782487 S.Shevtsov, E.V.Petrotchenko, L.C.Pedersen, and M.Negishi (2003).
Crystallographic analysis of a hydroxylated polychlorinated biphenyl (OH-PCB) bound to the catalytic estrogen binding site of human estrogen sulfotransferase.
  Environ Health Perspect, 111, 884-888.
PDB code: 1g3m
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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