ArticleProceedings of the National Academy of Sciences of the United States of America2006
A general binding mechanism for all human sulfatases by the formylglycine-generating enzyme.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 108 citations in OpenAlex.
- Cysteine Thioaldehydes: Photolytic Generation, Reactivity, and Biological Implications.Angewandte Chemie (International ed. in English) · 2026Article
- Sulfatase modifying factors control the timing of zebrafish convergence and extension morphogenesis.Nature communications · 2026Article
- Identification of Multiple Sulfatase Deficiency (MSD) in newborn screening: A case study.Molecular genetics and metabolism reports · 2026Article
- Effects of Arylsulfatase B and Pembrolizumab in combination on progression of metastatic melanoma in the B16F10 syngeneic mouse model.Frontiers in oncology · 2026Article
- Sulfatase modifying factors control the timing of zebrafish convergence and extension morphogenesis.bioRxiv : the preprint server for biology · 2025Article
- Article
- Evolutionary adaptation from hydrolytic to oxygenolytic catalysis at the α/β-hydrolase fold.Chemical science · 2023Article
- New Insights into theJournal of agricultural and food chemistry · 2023Review
- Increased Cerebral Serum Amyloid A2 and Parameters of Oxidation in Arylsulfatase B (N-Acetylgalactosamine-4-Sulfatase)-Null Mice.bioRxiv : the preprint server for biology · 2023Article
- Increased Cerebral Serum Amyloid A2 and Parameters of Oxidation in Arylsulfatase B (N-Acetylgalactosamine-4-Sulfatase)-Null Mice.Journal of Alzheimer's disease reports · 2023Article
- Profound Impact of Decline in N-Acetylgalactosamine-4-Sulfatase (Arylsulfatase B) on Molecular Pathophysiology and Human Diseases.International journal of molecular sciences · 2022Review
- Metagenomic, (bio)chemical, and microscopic analyses reveal the potential for the cycling of sulfated EPS in Shark Bay pustular mats.ISME communications · 2022Article
- Designed protein multimerization and polymerization for functionalization of proteins.Biotechnology letters · 2022Review
- Formylglycine-Generating Enzyme-Like Proteins Constitute a Novel Family of Widespread Type VI Secretion System Immunity Proteins.Journal of bacteriology · 2021Article
- Review
- Ancestral lysosomal enzymes with increased activity harbor therapeutic potential for treatment of Hunter syndrome.iScience · 2021Article
- Multiple Sulfatase Deficiency: A Disease Comprising Mucopolysaccharidosis, Sphingolipidosis, and More Caused by a Defect in Posttranslational Modification.International journal of molecular sciences · 2020Review
- Structure of formylglycine-generating enzyme in complex with copper and a substrate reveals an acidic pocket for binding and activation of molecular oxygen.Chemical science · 2019Article
- Metabolic functions of the human gut microbiota: the role of metalloenzymes.Natural product reports · 2019Review
- Formylglycine-generating enzyme binds substrate directly at a mononuclear Cu(I) center to initiate OProceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The formylglycine (FGly)-generating enzyme (FGE) uses molecular oxygen to oxidize a conserved cysteine residue in all eukaryotic sulfatases to the catalytically active FGly. Sulfatases degrade and remodel sulfate esters, and inactivity of FGE results in multiple sulfatase deficiency, a fatal disease. The previously determined FGE crystal structure revealed two crucial cysteine residues in the active site, one of which was thought to be implicated in substrate binding. The other cysteine residue partakes in a novel oxygenase mechanism that does not rely on any cofactors. Here, we present crystal structures of the individual FGE cysteine mutants and employ chemical probing of wild-type FGE, which defined the cysteines to differ strongly in their reactivity. This striking difference in reactivity is explained by the distinct roles of these cysteine residues in the catalytic mechanism. Hitherto, an enzyme-substrate complex as an essential cornerstone for the structural evaluation of the FGly formation mechanism has remained elusive. We also present two FGE-substrate complexes with pentamer and heptamer peptides that mimic sulfatases. The peptides isolate a small cavity that is a likely binding site for molecular oxygen and could host reactive oxygen intermediates during cysteine oxidation. Importantly, these FGE-peptide complexes directly unveil the molecular bases of FGE substrate binding and specificity. Because of the conserved nature of FGE sequences in other organisms, this binding mechanism is of general validity. Furthermore, several disease-causing mutations in both FGE and sulfatases are explained by this binding mechanism.
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