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PDBsum entry 2g3f
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References listed in PDB file
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Key reference
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Title
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A catalytic mechanism revealed by the crystal structures of the imidazolonepropionase from bacillus subtilis.
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Authors
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Y.Yu,
Y.H.Liang,
E.Brostromer,
J.M.Quan,
S.Panjikar,
Y.H.Dong,
X.D.Su.
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Ref.
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J Biol Chem, 2006,
281,
36929-36936.
[DOI no: ]
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PubMed id
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Abstract
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Imidazolonepropionase (EC 3.5.2.7) catalyzes the third step in the universal
histidine degradation pathway, hydrolyzing the carbon-nitrogen bonds in
4-imidazolone-5-propionic acid to yield N-formimino-l-glutamic acid. Here we
report the crystal structures of the Bacillus subtilis imidazolonepropionase and
its complex at 2.0-A resolution with substrate analog imidazole-4-acetic acid
sodium (I4AA). The structure of the native enzyme contains two domains, a TIM
(triose-phosphate isomerase) barrel domain with two insertions and a small
beta-sandwich domain. The TIM barrel domain is quite similar to the members of
the alpha/beta barrel metallo-dependent hydrolase superfamily, especially to
Escherichia coli cytosine deaminase. A metal ion was found in the central cavity
of the TIM barrel and was tightly coordinated to residues His-80, His-82,
His-249, Asp-324, and a water molecule. X-ray fluorescence scan analysis
confirmed that the bound metal ion was a zinc ion. An acetate ion, 6 A away from
the zinc ion, was also found in the potential active site. In the complex
structure with I4AA, a substrate analog, I4AA replaced the acetate ion and
contacted with Arg-89, Try-102, Tyr-152, His-185, and Glu-252, further defining
and confirming the active site. The detailed structural studies allowed us to
propose a zinc-activated nucleophilic attack mechanism for the hydrolysis
reaction catalyzed by the enzyme.
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Figure 1.
FIGURE 1. A, the chemical reaction catalyzed by the
imidazolonepropionase. B, imidazole-4-acetic acid sodium salt,
an analog of 4-imidazolone-5-propionic acid (the substrate of
imidazolonepropionase).
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Figure 4.
FIGURE 4. The schematic diagram of a proposed mechanism for
the hydrolysis reaction catalyzed by the family of
imidazolonepropionase (see under "Results and Discussion").
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2006,
281,
36929-36936)
copyright 2006.
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