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PDBsum entry 1v4t
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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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Structural basis for allosteric regulation of the monomeric allosteric enzyme human glucokinase.
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Authors
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K.Kamata,
M.Mitsuya,
T.Nishimura,
J.Eiki,
Y.Nagata.
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Ref.
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Structure, 2004,
12,
429-438.
[DOI no: ]
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PubMed id
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Abstract
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Glucokinase is a monomeric enzyme that displays a low affinity for glucose and a
sigmoidal saturation curve for its substrate, two properties that are important
for its playing the role of a glucose sensor in pancreas and liver. The
molecular basis for these two properties is not well understood. Herein we
report the crystal structures of glucokinase in its active and inactive forms,
which demonstrate that global conformational change, including domain
reorganization, is induced by glucose binding. This suggests that the positive
cooperativity of monomeric glucokinase obeys the "mnemonical
mechanism" rather than the well-known concerted model. These structures
also revealed an allosteric site through which small molecules may modulate the
kinetic properties of the enzyme. This finding provided the mechanistic basis
for activation of glucokinase as a potential therapeutic approach for treating
type 2 diabetes mellitus.
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Figure 6.
Figure 6. Kinetic Model of GlucokinaseGlucokinase appears
to exist in three conformations and to have two catalytic
cycles. The ratio of two catalytic cycles is responsible for the
sigmoidal response to glucose. Although ordered process in the
slow cycle of glucokinase was indicated by isotope-exchange
experiment, the addition of substrates in the fast cycle may be
random.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2004,
12,
429-438)
copyright 2004.
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