1Y4J

Crystal structure of the paralogue of the human formylglycine generating enzyme

Summary for 1Y4J

• Entry DOI: 10.2210/pdb1y4j/pdb
• Related: 1y1e 1y1f 1y1g 1y1h 1y1i 1y1j
• Descriptor: Sulfatase modifying factor 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: formylglycine, sulfatases, multiple sulfatase deficiency, homodimer, duf323, sugar binding protein
• Biological source: Homo sapiens (human)
• Cellular location: Endoplasmic reticulum lumen : Q8NBJ7
• Total number of polymer chains: 2
• Total formula weight: 65823.20

Authors

Dickmanns, A.,Rudolph, M.G.,Ficner, R. (deposition date: 2004-12-01, release date: 2005-02-08, Last modification date: 2024-11-13)

Primary citation

Dickmanns, A.,Schmidt, B.,Rudolph, M.G.,Mariappan, M.,Dierks, T.,von Figura, K.,Ficner, R.
Crystal Structure of Human pFGE, the Paralog of the C{alpha}-formylglycine-generating Enzyme
J.Biol.Chem., 280:15180-15187, 2005

PubMed Abstract: 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.

PubMed: 15687489
DOI: 10.1074/jbc.M414317200

Experimental method

X-RAY DIFFRACTION (1.864 Å)