Regulation of Muscle Glycogen Phospfaorylase by Physiological Effectors

The enzyme from rabbit skeletal muscle contains 842 amino acid residues and the essential cofactor pyridoxa1-5’-phosphate is linked through its aldehyde group to the &amino group of Lys680. The polypeptide chain can be divided in two domains, both of them having an-sheet core surrounded by a-helices. The main oligomeric form of the enzyme is a dimer. The interactions between identical subunits are relatively few in dephosphorylated form of the enzyme (phosphorylase b). The main contacts involve the cap (residues 36 to 45) and the tower (residues 260 to 276) of symmetryrelated subunits. X-ray crystallographic studies reveal four ligand-binding sites: catalytic site, allosteric effector site, glycogen storage site, and nucleoside inhibitor site (Figure 11.1). The catalytic site is buried in the centre of the subunit where the domains come together. Access to this site is achieved through a narrow channel which is some 1.2 nm long. The access is restricted mostly by the 280s loop (residues 282 to 286). The residues from the 280s loop are displaced upon transition to catalytically active state following motion of the symmetry-related towers. The allosteric effector site is located near the subunit interface and is separated by a distance of 3.2 nm from the catalytic site. The glycogen storage site is 3.0 nm apart from the catalytic site and at a distance of 4.0 urn from the allosteric effector site. The