PDBsum entry 1p49

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Hydrolase PDB id
Protein chain
549 a.a. *
BOG ×2
NAG ×2
Waters ×130
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Structure of human placental estrone/dhea sulfatase
Structure: Steryl-sulfatase. Chain: a. Synonym: steroid sulfatase, steryl-sulfate sulfohydrolase, arylsulfatasE C, asc. Ec:
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: placenta
2.60Å     R-factor:   0.254     R-free:   0.301
Authors: F.G.Hernandez-Guzman,T.Higashiyama,W.Pangborn,Y.Osawa,D.Ghos
Key ref:
F.G.Hernandez-Guzman et al. (2003). Structure of human estrone sulfatase suggests functional roles of membrane association. J Biol Chem, 278, 22989-22997. PubMed id: 12657638 DOI: 10.1074/jbc.M211497200
21-Apr-03     Release date:   12-Aug-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P08842  (STS_HUMAN) -  Steryl-sulfatase
583 a.a.
549 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.  - Steryl-sulfatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 3-beta-hydroxyandrost-5-en-17-one 3-sulfate + H2O = 3-beta- hydroxyandrost-5-en-17-one + sulfate
3-beta-hydroxyandrost-5-en-17-one 3-sulfate
+ H(2)O
= 3-beta- hydroxyandrost-5-en-17-one
+ sulfate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   10 terms 
  Biological process     metabolic process   11 terms 
  Biochemical function     catalytic activity     5 terms  


DOI no: 10.1074/jbc.M211497200 J Biol Chem 278:22989-22997 (2003)
PubMed id: 12657638  
Structure of human estrone sulfatase suggests functional roles of membrane association.
F.G.Hernandez-Guzman, T.Higashiyama, W.Pangborn, Y.Osawa, D.Ghosh.
Estrone sulfatase (ES; 562 amino acids), one of the key enzymes responsible for maintaining high levels of estrogens in breast tumor cells, is associated with the membrane of the endoplasmic reticulum (ER). The structure of ES, purified from the microsomal fraction of human placentas, has been determined at 2.60-A resolution by x-ray crystallography. This structure shows a domain consisting of two antiparallel alpha-helices that protrude from the roughly spherical molecule, thereby giving the molecule a "mushroom-like" shape. These highly hydrophobic helices, each about 40 A long, are capable of traversing the membrane, thus presumably anchoring the functional domain on the membrane surface facing the ER lumen. The location of the transmembrane domain is such that the opening to the active site, buried deep in a cavity of the "gill" of the "mushroom," rests near the membrane surface, thereby suggesting a role of the lipid bilayer in catalysis. This simple architecture could be a prototype utilized by the ER membrane in dictating the form and the function of ER-resident enzymes.
  Selected figure(s)  
Figure 4.
FIG. 4. a, active site catalytic residues and the coordination of Ca^2^+ as described under "Results." The catalytic residue FGS75 is shown with its final (2F[o] - F[c]) electron density contoured at 1.5 . b, a view of the active site showing an E1-SO[4] molecule covalently linked to FGS75 in an intermediate step. The model was achieved by superimposing the crystallographically observed sulfate moiety with that of E1-SO[4]. Residues that may have contacts with the steroid molecule and the residues that line the opening to the lipid bilayer (shown by the arrow) are also illustrated. c, a BOG molecule partially shields the solvent-exposed surface of transmembrane helices. The (2F[o] - F[c]) electron density is contoured at 1.0 .
Figure 5.
FIG. 5. A schematic diagram showing steps involved in the proposed reaction mechanism.
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 22989-22997) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19808095 D.Ghosh, J.Griswold, M.Erman, and W.Pangborn (2010).
X-ray structure of human aromatase reveals an androgen-specific active site.
  J Steroid Biochem Mol Biol, 118, 197-202.  
20814163 J.Matsumoto, N.Ariyoshi, I.Ishii, and M.Kitada (2010).
Six novel single nucleotide polymorphisms of the steroid sulfatase gene in a Japanese population.
  Drug Metab Pharmacokinet, 25, 403-407.  
19826804 K.McLuskey, A.W.Roszak, Y.Zhu, and N.W.Isaacs (2010).
Crystal structures of all-alpha type membrane proteins.
  Eur Biophys J, 39, 723-755.  
20165970 M.Buono, and M.P.Cosma (2010).
Sulfatase activities towards the regulation of cell metabolism and signaling in mammals.
  Cell Mol Life Sci, 67, 769-780.  
20632362 P.M.Wood, L.W.Woo, J.R.Labrosse, M.P.Thomas, M.F.Mahon, S.K.Chander, A.Purohit, M.J.Reed, and B.V.Potter (2010).
Bicyclic derivatives of the potent dual aromatase-steroid sulfatase inhibitor 2-bromo-4-{[(4-cyanophenyl)(4h-1,2,4-triazol-4-yl)amino]methyl}phenylsulfamate: synthesis, SAR, crystal structure, and in vitro and in vivo activities.
  ChemMedChem, 5, 1577-1593.  
20644568 S.X.Lin, J.Chen, M.Mazumdar, D.Poirier, C.Wang, A.Azzi, and M.Zhou (2010).
Molecular therapy of breast cancer: progress and future directions.
  Nat Rev Endocrinol, 6, 485-493.  
19289056 O.Tastan, J.Klein-Seetharaman, and H.Meirovitch (2009).
The effect of loops on the structural organization of alpha-helical membrane proteins.
  Biophys J, 96, 2299-2312.  
19520866 R.Tang, and S.D.Rosen (2009).
Functional consequences of the subdomain organization of the sulfs.
  J Biol Chem, 284, 21505-21514.  
19466699 V.Ahmed, Y.Liu, and S.D.Taylor (2009).
Multiple pathways for the irreversible inhibition of steroid sulfatase with quinone methide-generating suicide inhibitors.
  Chembiochem, 10, 1457-1461.  
18288656 P.Bojarová, E.Denehy, I.Walker, K.Loft, D.P.De Souza, L.W.Woo, B.V.Potter, M.J.McConville, and S.J.Williams (2008).
Direct evidence for ArO-S bond cleavage upon inactivation of Pseudomonas aeruginosa arylsulfatase by aryl sulfamates.
  Chembiochem, 9, 613-623.  
18625336 P.Bojarová, and S.J.Williams (2008).
Sulfotransferases, sulfatases and formylglycine-generating enzymes: a sulfation fascination.
  Curr Opin Chem Biol, 12, 573-581.  
17662596 J.L.Falany, and C.N.Falany (2007).
Interactions of the human cytosolic sulfotransferases and steroid sulfatase in the metabolism of tibolone and raloxifene.
  J Steroid Biochem Mol Biol, 107, 202-210.  
17728860 T.Jackson, L.W.Woo, M.N.Trusselle, S.K.Chander, A.Purohit, M.J.Reed, and B.V.Potter (2007).
Dual aromatase-sulfatase inhibitors based on the anastrozole template: synthesis, in vitro SAR, molecular modelling and in vivo activity.
  Org Biomol Chem, 5, 2940-2952.  
17045481 S.R.Hanson, L.J.Whalen, and C.H.Wong (2006).
Synthesis and evaluation of general mechanism-based inhibitors of sulfatases based on (difluoro)methyl phenyl sulfate and cyclic phenyl sulfamate motifs.
  Bioorg Med Chem, 14, 8386-8395.  
16124866 G.Diez-Roux, and A.Ballabio (2005).
Sulfatases and human disease.
  Annu Rev Genomics Hum Genet, 6, 355-379.  
15478125 J.Y.Winum, A.Scozzafava, J.L.Montero, and C.T.Supuran (2005).
Sulfamates and their therapeutic potential.
  Med Res Rev, 25, 186-228.  
16132094 Y.Liu, V.Ahmed, B.Hill, and S.D.Taylor (2005).
Synthesis of a non-hydrolyzable estrone sulfate analogue bearing the difluoromethanesulfonamide group and its evaluation as a steroid sulfatase inhibitor.
  Org Biomol Chem, 3, 3329-3335.  
15090207 A.Billich, M.Bilban, N.C.Meisner, P.Nussbaumer, A.Neubauer, S.Jäger, and M.Auer (2004).
Confocal fluorescence detection expanded to UV excitation: the first continuous fluorimetric assay of human steroid sulfatase in nanoliter volume.
  Assay Drug Dev Technol, 2, 21-30.  
15493058 S.R.Hanson, M.D.Best, and C.H.Wong (2004).
Sulfatases: structure, mechanism, biological activity, inhibition, and synthetic utility.
  Angew Chem Int Ed Engl, 43, 5736-5763.  
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.