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PDBsum entry 1fpi
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Hydrolase (phosphoric monoester)
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PDB id
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1fpi
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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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Crystallographic evidence for the action of potassium, Thallium, And lithium ions on fructose-1,6-Bisphosphatase.
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Authors
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V.Villeret,
S.Huang,
H.J.Fromm,
W.N.Lipscomb.
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Ref.
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Proc Natl Acad Sci U S A, 1995,
92,
8916-8920.
[DOI no: ]
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PubMed id
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Abstract
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Fructose-1,6-bisphosphatase (Fru-1,6-Pase; D-fructose-1,6-bisphosphate
1-phosphohydrolase, EC 3.1.3.11) requires two divalent metal ions to hydrolyze
alpha-D-fructose 1,6-bisphosphate. Although not required for catalysis,
monovalent cations modify the enzyme activity; K+ and Tl+ ions are activators,
whereas Li+ ions are inhibitors. Their mechanisms of action are still unknown.
We report here crystallographic structures of pig kidney Fru-1,6-Pase complexed
with K+, Tl+, or both Tl+ and Li+. In the T form Fru-1,6-Pase complexed with the
substrate analogue 2,5-anhydro-D-glucitol 1,6-bisphosphate (AhG-1,6-P2) and Tl+
or K+ ions, three Tl+ or K+ binding sites are found. Site 1 is defined by
Glu-97, Asp-118, Asp-121, Glu-280, and a 1-phosphate oxygen of AhG-1,6-P2; site
2 is defined by Glu-97, Glu-98, Asp-118, and Leu-120. Finally, site 3 is defined
by Arg-276, Glu-280, and the 1-phosphate group of AhG-1,6-P2. The Tl+ or K+ ions
at sites 1 and 2 are very close to the positions previously identified for the
divalent metal ions. Site 3 is specific to K+ or Tl+. In the divalent metal ion
complexes, site 3 is occupied by the guanidinium group of Arg-276. These
observations suggest that Tl+ or K+ ions can substitute for Arg-276 in the
active site and polarize the 1-phosphate group, thus facilitating nucleophilic
attack on the phosphorus center. In the T form complexed with both Tl+ and Li+
ions, Li+ replaces Tl+ at metal site 1. Inhibition by lithium very likely occurs
as it binds to this site, thus retarding turnover or phosphate release. The
present study provides a structural basis for a similar mechanism of inhibition
for inositol monophosphatase, one of the potential targets of lithium ions in
the treatment of manic depression.
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Secondary reference #1
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Title
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Structural aspects of the allosteric inhibition of fructose-1,6-Bisphosphatase by AMP: the binding of both the substrate analogue 2,5-Anhydro-D-Glucitol 1,6-Bisphosphate and catalytic metal ions monitored by X-Ray crystallography.
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Authors
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V.Villeret,
S.Huang,
Y.Zhang,
W.N.Lipscomb.
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Ref.
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Biochemistry, 1995,
34,
4307-4315.
[DOI no: ]
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PubMed id
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Secondary reference #2
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Title
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Structural similarities between fructose-1,6-Bisphosphatase and inositol monophosphatase.
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Authors
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Y.Zhang,
J.Y.Liang,
W.N.Lipscomb.
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Ref.
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Biochem Biophys Res Commun, 1993,
190,
1080-1083.
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PubMed id
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Secondary reference #3
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Title
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Crystallographic studies of the catalytic mechanism of the neutral form of fructose-1,6-Bisphosphatase.
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Authors
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Y.Zhang,
J.Y.Liang,
S.Huang,
H.Ke,
W.N.Lipscomb.
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Ref.
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Biochemistry, 1993,
32,
1844-1857.
[DOI no: ]
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PubMed id
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