Phosphorylase glycogen structure

FIGURE 15.15 (a) The structure of a glycogen phosphorylase monomer, showing the locations of the catalytic site, the PLP cofactor site, the allosteric effector site, the glycogen storage site, the tower helix (residnes 262 throngh 278), and the snbnnit interface. 

Hajdu, J., Pombradi, V., Bot, C., and Friedrich, P. (1979) Structural changes in glycogen phosphorylase as revealed by cross-linking with bifunctional diimidates Phosphorylase b. Biochemistry 18, 4037-4041. 

Muscle glycogen phosphorylase is one of the most well studied enzymes and was also one of the first enzymes discovered to be controlled by reversible phosphorylation (by E.G. Krebs and E. Fischer in 1956). Phosphorylase is also controlled allosterically by ATP, AMP, glucose and glucose-6-phosphate. Structurally, muscle glycogen phosphorylase is similar to its hepatic isoenzyme counterpart composed of identical subunits each with a molecular mass of approximately 110 kDa. To achieve full activity, the enzyme requires the binding of one molecule of pyridoxal phosphate, the active form of vitamin B6, to each subunit. 

L. Nprskov-Lauritsen, and L. Agius, Iminosugars as potential inhibitors of glycogenolysis Structural insights into the molecular basis of glycogen phosphorylase inhibition,./. Med. Chem., 49 (2006) 5687-5701. 

The strict primer dependence of the glycogen phosphorylases makes them ideal candidates for the synthesis of hybrid structures of amylose with non-natural materials... 

Recently, the in vitro synthesis of amylopectin- or glycogen-like structures via a tandem reaction of phosphorylase and branching enzyme was reported [197-201]. 

Fig. 2.12. Structural changes at the N-terminus of glycogen phosphorylase as a result of phosphorylation. a) R-form of the dimer of glycogen phosphorylase a. b) T form of the dimer of glycogen phosphorylase b. Phosphorylation at Serl3 near the N-terminus transforms the inactive glycogen phosphorylase b into the active glycogen phosphorylase a. The N-terminus rearranges significantly as a result of phosphorylation. In the inactive T-state the N-terminus interacts with the same subunit, while in the R-form it forms interactions with the other subunit. After Barford and Johnson (1991), with permission.

The breakdown of glycogen in skeletal muscles and the liver is regulated by variations in the ratio of the two forms of glycogen phosphorylase. The a and b forms differ in their secondary, tertiary, and quaternary structures the active site undergoes changes in structure and, consequently, changes in catalytic activity as the two forms are interconverted. 

Clear discussion of the regulatory changes in the structure of glycogen phosphorylase, based on the structures (from x-ray diffraction studies) of the active and less active forms of the enzyme. 

Observation of an abnormally large shift in the position of fluorescent emission of pyridoxal phosphate (PLP) in glycogen phosphorylase answered an interesting chemical question.187188 A 330 nm (30,300 cm ) absorption band could be interpreted either as arising from an adduct of some enzyme functional group with the Schiff base of PLP and a lysine side chain (structure A) or as a nonionic tautomer of a Schiff base in a hydrophobic environment (structure B, Eq. 23-24). For structure A, the fluorescent emission would be expected at a position similar to that of pyridoxamine. On the other hand, Schiff bases of the... 

In a second class of regulatory enzymes the active and inactive forms are inter-converted by covalent modifications of their structures by enzymes. The classic example of this type of control is the use of glycogen phosphorylase from animal tissues to catalyse the breakdown of the polysaccharide glycogen yielding glucose-1-phosphate, as illustrated in Fig. 5.37. 

Residues in the region of the substrate-binding site for phosphate in phosphorylase b in the T state (a) and the R state (b). The side chain of Asp 283 leaves the binding site in the R structure, and the side chain of Arg 569 becomes available to interact with the phosphate. Key side chains and bound phosphate anion are shown in red. Portions of the polypeptide backbone are drawn in heavy black. (Source From D. Barford and L. N. Johnson, The allosteric transition of glycogen phosphorylase, Nature 340 609, 1989.)... 

Sprang, S. R., et al., Structural changes in glycogen phosphorylase induced by phosphorylation. Nature 336 215, 1988. 

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