PMID: 15687489

 

    Legend: Sugar

Title : Crystal structure of human pFGE , the paralog of the Calpha- formylglycine-generating enzyme

Abstract :

1. In eukaryotes, sulfate esters are degraded by sulfatases, which possess a unique Calpha-formylglycine residue in their active site
2. The defect in post-translational formation of the Calpha-formylglycine residue causes a severe lysosomal storage disorder in humans
3. Recently, FGE ( formylglycine-generating enzyme ) has been identified as the protein required for this specific modification
4. Using sequence comparisons, a protein homologous to FGE was found and denoted pFGE (paralog of FGE )
5. pFGE binds a sulfatase-derived peptide bearing the FGE recognition motif , but it lacks formylglycine-generating activity
6. 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
7. We have crystallized the glycosylated human pFGE and determined its crystal structure at a resolution of 1.86 A
8. The structure reveals a novel fold, which we denote the FGE fold and which therefore serves as a paradigm for the DUF323 domain
9. It is characterized by an asymmetric partitioning of secondary structure elements and is stabilized by two calcium cations
10. A deep cleft on the surface of pFGE most likely represents the sulfatase polypeptide binding site
11. The asymmetric unit of the pFGE crystal contains a homodimer
12. The putative peptide binding site is buried between the monomers, indicating a biological significance of the dimer
13. The structure suggests the capability of pFGE to form a heterodimer with FGE