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PDBsum entry 1y1e
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Oxidoreductase
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PDB id
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1y1e
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References listed in PDB file
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Key reference
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Title
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Molecular basis for multiple sulfatase deficiency and mechanism for formylglycine generation of the human formylglycine-Generating enzyme.
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Authors
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T.Dierks,
A.Dickmanns,
A.Preusser-Kunze,
B.Schmidt,
M.Mariappan,
K.Von figura,
R.Ficner,
M.G.Rudolph.
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Ref.
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Cell, 2005,
121,
541-552.
[DOI no: ]
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PubMed id
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Abstract
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Sulfatases are enzymes essential for degradation and remodeling of sulfate
esters. Formylglycine (FGly), the key catalytic residue in the active site, is
unique to sulfatases. In higher eukaryotes, FGly is generated from a cysteine
precursor by the FGly-generating enzyme (FGE). Inactivity of FGE results in
multiple sulfatase deficiency (MSD), a fatal autosomal recessive syndrome. Based
on the crystal structure, we report that FGE is a single-domain monomer with a
surprising paucity of secondary structure and adopts a unique fold. The effect
of all 18 missense mutations found in MSD patients is explained by the FGE
structure, providing a molecular basis of MSD. The catalytic mechanism of FGly
generation was elucidated by six high-resolution structures of FGE in different
redox environments. The structures allow formulation of a novel oxygenase
mechanism whereby FGE utilizes molecular oxygen to generate FGly via a cysteine
sulfenic acid intermediate.
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Figure 2.
Figure 2. Comparison of FGE and pFGE
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Figure 6.
Figure 6. Molecular Basis of Multiple Sulfatase Deficiency
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2005,
121,
541-552)
copyright 2005.
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