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PDBsum entry 1fc0
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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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Activation of human liver glycogen phosphorylase by alteration of the secondary structure and packing of the catalytic core.
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Authors
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V.L.Rath,
M.Ammirati,
P.K.Lemotte,
K.F.Fennell,
M.N.Mansour,
D.E.Danley,
T.R.Hynes,
G.K.Schulte,
D.J.Wasilko,
J.Pandit.
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Ref.
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Mol Cell, 2000,
6,
139-148.
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PubMed id
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Abstract
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Glycogen phosphorylases catalyze the breakdown of glycogen to
glucose-1-phosphate, which enters glycolysis to fulfill the energetic
requirements of the organism. Maintaining control of blood glucose levels is
critical in minimizing the debilitating effects of diabetes, making liver
glycogen phosphorylase a potential therapeutic target. To support inhibitor
design, we determined the crystal structures of the active and inactive forms of
human liver glycogen phosphorylase a. During activation, forty residues of the
catalytic site undergo order/disorder transitions, changes in secondary
structure, or packing to reorganize the catalytic site for substrate binding and
catalysis. Knowing the inactive and active conformations of the liver enzyme and
how each differs from its counterpart in muscle phosphorylase provides the basis
for designing inhibitors that bind preferentially to the inactive conformation
of the liver isozyme.
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