| Structural highlights
1y4j is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Related: | 1y1e, 1y1f, 1y1g, 1y1h, 1y1i, 1y1j |
| Gene: | SUMF2 (HUMAN) |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Function
[SUMF2_HUMAN] Lacks formyl-glycine generating activity and is unable to convert newly synthesized inactive sulfatases to their active form. Inhibits the activation of sulfatases by SUMF1.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
In eukaryotes, sulfate esters are degraded by sulfatases, which possess a unique Calpha-formylglycine residue in their active site. The defect in post-translational formation of the Calpha-formylglycine residue causes a severe lysosomal storage disorder in humans. Recently, FGE (formylglycine-generating enzyme) has been identified as the protein required for this specific modification. Using sequence comparisons, a protein homologous to FGE was found and denoted pFGE (paralog of FGE). pFGE binds a sulfatase-derived peptide bearing the FGE recognition motif, but it lacks formylglycine-generating activity. Both proteins belong to a large family of pro- and eukaryotic proteins containing the DUF323 domain, a formylglycine-generating enzyme domain of unknown three-dimensional structure. We have crystallized the glycosylated human pFGE and determined its crystal structure at a resolution of 1.86 A. The structure reveals a novel fold, which we denote the FGE fold and which therefore serves as a paradigm for the DUF323 domain. It is characterized by an asymmetric partitioning of secondary structure elements and is stabilized by two calcium cations. A deep cleft on the surface of pFGE most likely represents the sulfatase polypeptide binding site. The asymmetric unit of the pFGE crystal contains a homodimer. The putative peptide binding site is buried between the monomers, indicating a biological significance of the dimer. The structure suggests the capability of pFGE to form a heterodimer with FGE.
Crystal structure of human pFGE, the paralog of the Calpha-formylglycine-generating enzyme.,Dickmanns A, Schmidt B, Rudolph MG, Mariappan M, Dierks T, von Figura K, Ficner R J Biol Chem. 2005 Apr 15;280(15):15180-7. Epub 2005 Feb 1. PMID:15687489[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cosma MP, Pepe S, Annunziata I, Newbold RF, Grompe M, Parenti G, Ballabio A. The multiple sulfatase deficiency gene encodes an essential and limiting factor for the activity of sulfatases. Cell. 2003 May 16;113(4):445-56. PMID:12757706
- ↑ Mariappan M, Preusser-Kunze A, Balleininger M, Eiselt N, Schmidt B, Gande SL, Wenzel D, Dierks T, von Figura K. Expression, localization, structural, and functional characterization of pFGE, the paralog of the Calpha-formylglycine-generating enzyme. J Biol Chem. 2005 Apr 15;280(15):15173-9. Epub 2005 Feb 11. PMID:15708861 doi:http://dx.doi.org/10.1074/jbc.M413698200
- ↑ Zito E, Fraldi A, Pepe S, Annunziata I, Kobinger G, Di Natale P, Ballabio A, Cosma MP. Sulphatase activities are regulated by the interaction of sulphatase-modifying factor 1 with SUMF2. EMBO Rep. 2005 Jul;6(7):655-60. PMID:15962010 doi:http://dx.doi.org/7400454
- ↑ Dickmanns A, Schmidt B, Rudolph MG, Mariappan M, Dierks T, von Figura K, Ficner R. Crystal structure of human pFGE, the paralog of the Calpha-formylglycine-generating enzyme. J Biol Chem. 2005 Apr 15;280(15):15180-7. Epub 2005 Feb 1. PMID:15687489 doi:10.1074/jbc.M414317200
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