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PDBsum entry 1hdh
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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1.3 a structure of arylsulfatase from pseudomonas aeruginosa establishes the catalytic mechanism of sulfate ester cleavage in the sulfatase family.
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Authors
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I.Boltes,
H.Czapinska,
A.Kahnert,
R.Von bülow,
T.Dierks,
B.Schmidt,
K.Von figura,
M.A.Kertesz,
I.Usón.
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Ref.
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Structure, 2001,
9,
483-491.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Sulfatases constitute a family of enzymes with a highly conserved
active site region including a Calpha-formylglycine that is posttranslationally
generated by the oxidation of a conserved cysteine or serine residue. The
crystal structures of two human arylsulfatases, ASA and ASB, along with ASA
mutants and their complexes led to different proposals for the catalytic
mechanism in the hydrolysis of sulfate esters. RESULTS: The crystal structure of
a bacterial sulfatase from Pseudomonas aeruginosa (PAS) has been determined at
1.3 A. Fold and active site region are strikingly similar to those of the known
human sulfatases. The structure allows a precise determination of the active
site region, unequivocally showing the presence of a Calpha-formylglycine
hydrate as the key catalytic residue. Furthermore, the cation located in the
active site is unambiguously characterized as calcium by both its B value and
the geometry of its coordination sphere. The active site contains a
noncovalently bonded sulfate that occupies the same position as the one in
para-nitrocatecholsulfate in previously studied ASA complexes. CONCLUSIONS: The
structure of PAS shows that the resting state of the key catalytic residue in
sulfatases is a formylglycine hydrate. These structural data establish a
mechanism for sulfate ester cleavage involving an aldehyde hydrate as the
functional group that initiates the reaction through a nucleophilic attack on
the sulfur atom in the substrate. The alcohol is eliminated from a reaction
intermediate containing pentacoordinated sulfur. Subsequent elimination of the
sulfate regenerates the aldehyde, which is again hydrated. The metal cation
involved in stabilizing the charge and anchoring the substrate during catalysis
is established as calcium.
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Figure 5.
Figure 5. A scheme of the Proposed Catalytic Mechanism
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2001,
9,
483-491)
copyright 2001.
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