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Figure 3.
Substrate binding and mechanistic details. (a) Hydrogen
bonds are shown as dashed lines, and water molecules are drawn
as red spheres. (b) General binding mechanism of FGE to all
human sulfatases. The schematic drawing generalizes the binding
of unfolded sulfatases to FGE as the first step in FGly
formation. (c) Magnification of the region adjacent to the
intermolecular disulfide bond. The orientation of the Tyr-340
side chain in the apo– and peptide–FGE structures differs by
6.4 Å (compare with Fig. 4). Only residues Cys-P69 and
Thr-P70 of the peptide are drawn. The solvent-inaccessible
volume between the disulfide bond and serine residues 333 and
336 (transparent gray sphere) is occupied by Cl^– (green) in
the complex structure. (d) Possible mechanisms after the
activation of molecular oxygen by FGE. Atoms from O[2] are
indicated in red. A novel hydroperoxide intermediate is
formulated from which two alternative avenues for FGly formation
are conceivable. Currently, no distinction between these two
pathways is possible.
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