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PDBsum entry 1x7n
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References listed in PDB file
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Key reference
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Title
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The structures of inhibitor complexes of pyrococcus furiosus phosphoglucose isomerase provide insights into substrate binding and catalysis.
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Authors
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J.M.Berrisford,
J.Akerboom,
S.Brouns,
S.E.Sedelnikova,
A.P.Turnbull,
J.Van der oost,
L.Salmon,
R.Hardré,
I.A.Murray,
G.M.Blackburn,
D.W.Rice,
P.J.Baker.
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Ref.
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J Mol Biol, 2004,
343,
649-657.
[DOI no: ]
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PubMed id
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Abstract
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Pyrococcus furiosus phosphoglucose isomerase (PfPGI) is a metal-containing
enzyme that catalyses the interconversion of glucose 6-phosphate (G6P) and
fructose 6-phosphate (F6P). The recent structure of PfPGI has confirmed the
hypothesis that the enzyme belongs to the cupin superfamily and identified the
position of the active site. This fold is distinct from the alphabetaalpha
sandwich fold commonly seen in phosphoglucose isomerases (PGIs) that are found
in bacteria, eukaryotes and some archaea. Whilst the mechanism of the latter
family is thought to proceed through a cis-enediol intermediate, analysis of the
structure of PfPGI in the presence of inhibitors has led to the suggestion that
the mechanism of this enzyme involves the metal-dependent direct transfer of a
hydride between C1 and C2 atoms of the substrate. To gain further insight in the
reaction mechanism of PfPGI, the structures of the free enzyme and the complexes
with the inhibitor, 5-phospho-d-arabinonate (5PAA) in the presence and absence
of metal have been determined. Comparison of these structures with those of
equivalent complexes of the eukaryotic PGIs reveals similarities at the active
site in the disposition of possible catalytic residues. These include the
presence of a glutamic acid residue, Glu97 in PfPGI, which occupies the same
position relative to the inhibitor as that of the glutamate that is thought to
function as the catalytic base in the eukaryal-type PGIs. These similarities
suggest that aspects of the catalytic mechanisms of these two structurally
unrelated PGIs may be similar and based on an enediol intermediate.
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Figure 1.
Figure 1. A schematic representation of the PfPGI dimer
viewed down the 2-fold axis. One subunit of the dimer is shown
in blue and red (strands and helices, respectively) and the
other in orange. The N-terminal strand can be seen to interact
with the adjacent symmetry-related strand from the other subunit
in the biological dimer.
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Figure 2.
Figure 2. A stereo diagram of the active site of PfPGI
showing the 2F[O] -F[C] map, contoured at 1s (blue) and 4s
(red), electron density assigned to 5PAA in the PfPGI/5PAA
metal-free complex and its interaction with Glu97. A blue line
shows the potential hydrogen bond between the carboxyl of Glu97
and the carboxyl of 5PAA.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2004,
343,
649-657)
copyright 2004.
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