2hib
human formylglycine generating enzyme, C336S mutant, iodide co-crystallization
Structural highlights
DiseaseSUMF1_HUMAN Defects in SUMF1 are the cause of multiple sulfatase deficiency (MSD) [MIM:272200. MSD is a clinically and biochemically heterogeneous disorder caused by the simultaneous impairment of all sulfatases, due to defective post-translational modification and activation. It combines features of individual sulfatase deficiencies such as metachromatic leukodystrophy, mucopolysaccharidosis, chondrodysplasia punctata, hydrocephalus, ichthyosis, neurologic deterioration and developmental delay. Inheritance is autosomal recessive.[1] [2] [3] [4] FunctionSUMF1_HUMAN Using molecular oxygen and an unidentified reducing agent, oxidizes a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue, which is also called C(alpha)-formylglycine. Known substrates include GALNS, ARSA, STS and ARSE.[5] [6] 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 PubMedThe catalytic residue in sulfatases is a unique formylglycine that is post-translationally generated by oxidation of a cysteine or serine precursor. Molecular oxygen oxidizes the cysteine precursor in eukaryotic sulfatases, a reaction that is catalysed by the formylglycine-generating enzyme FGE. Previously, FGE was crystallized in complex with a chloride ion which, based on its similar polarizability and hydrophobicity, indicates the site of molecular oxygen binding. Here, two structures of FGE in complex with bromide and iodide were determined in order to further delineate the volume and stereochemical restraints of the oxygen-binding site for potential reaction intermediates. Anomalous difference density maps unambiguously assigned the nature of the halide ions. Unexpectedly, data collected at a wavelength of 1.54 A from the iodide-containing crystal and data collected at a wavelength of 0.8 A from a bromide-containing crystal were sufficient for SIRAS phasing. Probing the oxygen-binding site of the human formylglycine-generating enzyme using halide ions.,Roeser D, Schmidt B, Preusser-Kunze A, Rudolph MG Acta Crystallogr D Biol Crystallogr. 2007 May;63(Pt 5):621-7. Epub 2007, Apr 21. PMID:17452787[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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