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PDBsum entry 1gpy
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Glycogen phosphorylase
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PDB id
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1gpy
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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 binding studies on the allosteric inhibitor glucose-6-Phosphate to t state glycogen phosphorylase b.
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Authors
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L.N.Johnson,
P.Snape,
J.L.Martin,
K.R.Acharya,
D.Barford,
N.G.Oikonomakos.
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Ref.
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J Mol Biol, 1993,
232,
253-267.
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PubMed id
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Abstract
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Glucose-6-phosphate is an important allosteric inhibitor of glycogen
phosphorylase b that restrains the enzyme in the inactive state in resting
muscle. A crystallographic binding study by diffusion of glucose-6-phosphate
into performed crystals of T state phosphorylase b has been carried out at 2.3 A
resolution and the structure refined by restrained crystallographic
least-squares and simulated annealing to give a crystallographic R-value of
0.203. The inhibitor binds at the AMP allosteric effector site at the
subunit-subunit interface of the dimer. The phosphate groups of the
glucose-6-phosphate and AMP occupy partially overlapping sites and make similar
contacts to two arginine residues (Arg309 and Arg310) but in glucose-6-phosphate
there is a contact to a third arginine (Arg242). The glucopyranose of
glucose-6-phosphate and the adenine ribose of AMP occupy different positions.
Including the contacts to the three arginine residues by the phosphate group,
the glucose-6-phosphate makes a total of 11 hydrogen-bonds to the enzyme and all
but one of these are to charged groups. The O-2 hydroxyl hydrogen-bonds to the
main-chain carbonyl oxygen of Val40' from the other subunit and this interaction
appears important for the allosteric response. There are substantial
conformational changes both in the vicinity of the glucose-6-phosphate
(involving for example Phe196 and Arg309) and at the subunit interface
(involving residues 42' to 51' and 192 to 196). These shifts tighten the binding
of the inhibitor and the interface. Comparison of the glucose-6-phosphate
complex with the T state native phosphorylase b and the R state phosphorylase a
structures shows that there is a graded response from T state
glucose-6-phosphate complex through T state phosphorylase b to R state
phosphorylase a that suggests that glucose-6-phosphate promotes a tight
structure that is more "tensed" than native T state phosphorylase b. The results
show how the same allosteric effector site can exhibit a tight binding site for
the activator AMP in the R state structure and a tight binding site for
glucose-6-phosphate in the modified T state structure.
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Secondary reference #1
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Title
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Glycogen phosphorylase b: description of the protein structure
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Authors
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K.R.Acharya,
D.I.Stuart,
K.M.Varvill,
L.N.Johnson.
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Ref.
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glycogen phosphorylase b: ...
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Secondary reference #2
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Title
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Structural mechanism for glycogen phosphorylase control by phosphorylation and AMP.
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Authors
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D.Barford,
S.H.Hu,
L.N.Johnson.
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Ref.
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J Mol Biol, 1991,
218,
233-260.
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PubMed id
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