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PDBsum entry 1y1e
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Oxidoreductase PDB id
1y1e

 

 

 

 

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Contents
Protein chain
272 a.a. *
Ligands
NAG
Metals
_CA ×2
Waters ×407
* Residue conservation analysis
PDB id:
1y1e
Name: Oxidoreductase
Title: Human formylglycine generating enzyme
Structure: C-alpha-formyglycine-generating enzyme. Chain: x. Fragment: residues 73-383. Synonym: fge. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: ht1080. Expression_system_cell: fibrosarcoma tumor cells
Resolution:
1.73Å     R-factor:   0.196     R-free:   0.242
Authors: M.G.Rudolph,A.Dickmanns,R.Ficner
Key ref:
T.Dierks et al. (2005). Molecular basis for multiple sulfatase deficiency and mechanism for formylglycine generation of the human formylglycine-generating enzyme. Cell, 121, 541-552. PubMed id: 15907468 DOI: 10.1016/j.cell.2005.03.001
Date:
18-Nov-04     Release date:   31-May-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q8NBK3  (SUMF1_HUMAN) -  Formylglycine-generating enzyme from Homo sapiens
Seq:
Struc: 		374 a.a.
272 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.8.3.7  - formylglycine-generating enzyme.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-cysteinyl-[sulfatase] + 2 a thiol + O2 = an organic disulfide + 3-oxo- L-alanyl-[sulfatase] + hydrogen sulfide + H2O + H+
L-cysteinyl-[sulfatase]
 + 2 × a thiol
 + O2
 = organic disulfide
 + 3-oxo- L-alanyl-[sulfatase]
 + hydrogen sulfide
 + H2O
 + H(+)
      Cofactor: Ca(2+); Cu cation
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Key reference    
 
 
DOI no: 10.1016/j.cell.2005.03.001 Cell 121:541-552 (2005)
PubMed id: 15907468  
 
 
Molecular basis for multiple sulfatase deficiency and mechanism for formylglycine generation of the human formylglycine-generating enzyme.
T.Dierks, A.Dickmanns, A.Preusser-Kunze, B.Schmidt, M.Mariappan, K.von Figura, R.Ficner, M.G.Rudolph.
 
  ABSTRACT  
 
Sulfatases are enzymes essential for degradation and remodeling of sulfate esters. Formylglycine (FGly), the key catalytic residue in the active site, is unique to sulfatases. In higher eukaryotes, FGly is generated from a cysteine precursor by the FGly-generating enzyme (FGE). Inactivity of FGE results in multiple sulfatase deficiency (MSD), a fatal autosomal recessive syndrome. Based on the crystal structure, we report that FGE is a single-domain monomer with a surprising paucity of secondary structure and adopts a unique fold. The effect of all 18 missense mutations found in MSD patients is explained by the FGE structure, providing a molecular basis of MSD. The catalytic mechanism of FGly generation was elucidated by six high-resolution structures of FGE in different redox environments. The structures allow formulation of a novel oxygenase mechanism whereby FGE utilizes molecular oxygen to generate FGly via a cysteine sulfenic acid intermediate.
 
  Selected figure(s)  
 
Figure 2.
Figure 2. Comparison of FGE and pFGE 		Figure 6.
Figure 6. Molecular Basis of Multiple Sulfatase Deficiency
 
  The above figures are reprinted by permission from Cell Press: Cell (2005, 121, 541-552) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21224894 L.Schlotawa, E.C.Ennemann, K.Radhakrishnan, B.Schmidt, A.Chakrapani, H.J.Christen, H.Moser, B.Steinmann, T.Dierks, and J.Gärtner (2011).
SUMF1 mutations affecting stability and activity of formylglycine generating enzyme predict clinical outcome in multiple sulfatase deficiency.
  Eur J Hum Genet, 19, 253-261.  
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.  
20973023 M.Schelwies, D.Brinson, S.Otsuki, Y.H.Hong, M.K.Lotz, C.H.Wong, and S.R.Hanson (2010).
Glucosamine-6-sulfamate analogues of heparan sulfate as inhibitors of endosulfatases.
  Chembiochem, 11, 2393-2397.  
20157809 S.Fetzner, and R.A.Steiner (2010).
Cofactor-independent oxidases and oxygenases.
  Appl Microbiol Biotechnol, 86, 791-804.  
19066960 A.Busche, J.B.Hennermann, F.Bürger, H.Proquitté, T.Dierks, A.von Arnim-Baas, and D.Horn (2009).
Neonatal manifestation of multiple sulfatase deficiency.
  Eur J Pediatr, 168, 969-973.  
19400797 F.Hsu, S.Schwarz, and J.D.Mougous (2009).
TagR promotes PpkA-catalysed type VI secretion activation in Pseudomonas aeruginosa.
  Mol Microbiol, 72, 1111-1125.  
19726671 J.R.Myette, V.Soundararajan, Z.Shriver, R.Raman, and R.Sasisekharan (2009).
Heparin/heparan sulfate 6-O-sulfatase from Flavobacterium heparinum: integrated structural and biochemical investigation of enzyme active site and substrate specificity.
  J Biol Chem, 284, 35177-35188.  
19130455 M.A.Frese, and T.Dierks (2009).
Formylglycine aldehyde Tag--protein engineering through a novel post-translational modification.
  Chembiochem, 10, 425-427.  
19675886 M.Sunbul, and J.Yin (2009).
Site specific protein labeling by enzymatic posttranslational modification.
  Org Biomol Chem, 7, 3361-3371.  
19697114 O.A.Artigalás, L.R.da Silva, M.Burin, G.M.Pastores, B.Zeng, N.Macedo, and I.V.Schwartz (2009).
Multiple sulfatase deficiency: clinical report and description of two novel mutations in a Brazilian patient.
  Metab Brain Dis, 24, 493-500.  
19224915 U.Matzner, B.Breiden, G.Schwarzmann, A.Yaghootfam, A.L.Fluharty, A.Hasilik, K.Sandhoff, and V.Gieselmann (2009).
Saposin B-dependent reconstitution of arylsulfatase A activity in vitro and in cell culture models of metachromatic leukodystrophy.
  J Biol Chem, 284, 9372-9381.  
18508857 A.Fraldi, E.Zito, F.Annunziata, A.Lombardi, M.Cozzolino, M.Monti, C.Spampanato, A.Ballabio, P.Pucci, R.Sitia, and M.P.Cosma (2008).
Multistep, sequential control of the trafficking and function of the multiple sulfatase deficiency gene product, SUMF1 by PDI, ERGIC-53 and ERp44.
  Hum Mol Genet, 17, 2610-2621.  
18390551 B.L.Carlson, E.R.Ballister, E.Skordalakes, D.S.King, M.A.Breidenbach, S.A.Gilmore, J.M.Berger, and C.R.Bertozzi (2008).
Function and structure of a prokaryotic formylglycine-generating enzyme.
  J Biol Chem, 283, 20117-20125.
PDB code: 2q17
18321157 G.A.Grabowski (2008).
Treatment perspectives for the lysosomal storage diseases.
  Expert Opin Emerg Drugs, 13, 197-211.  
18223294 K.Kaiserova, X.L.Tang, S.Srivastava, and A.Bhatnagar (2008).
Role of nitric oxide in regulating aldose reductase activation in the ischemic heart.
  J Biol Chem, 283, 9101-9112.  
18283100 M.A.Frese, S.Schulz, and T.Dierks (2008).
Arylsulfatase G, a novel lysosomal sulfatase.
  J Biol Chem, 283, 11388-11395.  
18178549 M.Mariappan, K.Radhakrishnan, T.Dierks, B.Schmidt, and K.von Figura (2008).
ERp44 mediates a thiol-independent retention of formylglycine-generating enzyme in the endoplasmic reticulum.
  J Biol Chem, 283, 6375-6383.  
18305113 M.Mariappan, S.L.Gande, K.Radhakrishnan, B.Schmidt, T.Dierks, and K.von Figura (2008).
The non-catalytic N-terminal extension of formylglycine-generating enzyme is required for its biological activity and retention in the endoplasmic reticulum.
  J Biol Chem, 283, 11556-11564.  
18625336 P.Bojarová, and S.J.Williams (2008).
Sulfotransferases, sulfatases and formylglycine-generating enzymes: a sulfation fascination.
  Curr Opin Chem Biol, 12, 573-581.  
18266766 S.L.Gande, M.Mariappan, B.Schmidt, T.H.Pringle, K.von Figura, and T.Dierks (2008).
Paralog of the formylglycine-generating enzyme--retention in the endoplasmic reticulum by canonical and noncanonical signals.
  FEBS J, 275, 1118-1130.  
18558715 T.L.Grove, K.H.Lee, J.St Clair, C.Krebs, and S.J.Booker (2008).
In vitro characterization of AtsB, a radical SAM formylglycine-generating enzyme that contains three [4Fe-4S] clusters.
  Biochemistry, 47, 7523-7538.  
17093507 C.Sevin, L.Verot, A.Benraiss, D.Van Dam, D.Bonnin, G.Nagels, F.Fouquet, V.Gieselmann, M.T.Vanier, P.P.De Deyn, P.Aubourg, and N.Cartier (2007).
Partial cure of established disease in an animal model of metachromatic leukodystrophy after intracerebral adeno-associated virus-mediated gene transfer.
  Gene Ther, 14, 405-414.  
17347913 C.Sevin, P.Aubourg, and N.Cartier (2007).
Enzyme, cell and gene-based therapies for metachromatic leukodystrophy.
  J Inherit Metab Dis, 30, 175-183.  
17452787 D.Roeser, B.Schmidt, A.Preusser-Kunze, and M.G.Rudolph (2007).
Probing the oxygen-binding site of the human formylglycine-generating enzyme using halide ions.
  Acta Crystallogr D Biol Crystallogr, 63, 621-627.
PDB codes: 2hi8 2hib
17446859 E.Zito, M.Buono, S.Pepe, C.Settembre, I.Annunziata, E.M.Surace, T.Dierks, M.Monti, M.Cozzolino, P.Pucci, A.Ballabio, and M.P.Cosma (2007).
Sulfatase modifying factor 1 trafficking through the cells: from endoplasmic reticulum to the endoplasmic reticulum.
  EMBO J, 26, 2443-2453.  
16368756 D.Roeser, A.Preusser-Kunze, B.Schmidt, K.Gasow, J.G.Wittmann, T.Dierks, K.von Figura, and M.G.Rudolph (2006).
A general binding mechanism for all human sulfatases by the formylglycine-generating enzyme.
  Proc Natl Acad Sci U S A, 103, 81-86.
PDB codes: 2aft 2afy 2aii 2aij 2aik
16317791 D.W.Heinz, M.S.Weiss, and K.U.Wendt (2006).
Biomacromolecular interactions, assemblies and machines: a structural view.
  Chembiochem, 7, 203-208.  
16766528 O.Berteau, A.Guillot, A.Benjdia, and S.Rabot (2006).
A new type of bacterial sulfatase reveals a novel maturation pathway in prokaryotes.
  J Biol Chem, 281, 22464-22470.  
17067361 S.Jean, C.Kasinathan, S.Buyske, and P.Manowitz (2006).
Ethanol decreases rat hepatic arylsulfatase A activity levels.
  Alcohol Clin Exp Res, 30, 1950-1955.  
16041070 D.Roeser, A.Dickmanns, K.Gasow, and M.G.Rudolph (2005).
De novo calcium/sulfur SAD phasing of the human formylglycine-generating enzyme using in-house data.
  Acta Crystallogr D Biol Crystallogr, 61, 1057-1066.
PDB code: 1z70
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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