Location of pyridoxal phosphate in glycogen phosphorylase a.
The pyridoxal 5'-phosphate cofactor of glycogen phosphorylase a (1,4-alpha-D-glucan:orthophosphate alpha-glucosyltransferase, EC2.4.1.1.) has been positioned on the protomer with x-ray diffraction data, chemical markers, and sequence information. The electron density was computed from 3.0-A resolution phases calculated from four heavy-atom derivatives. The cofactor is buried inside the protomer adjacent to the glucose-binding site. The phosphoryl substrates Pi and glucose-1-P each bind at two sites on the protomer. At low concentrations, Pi and glucose-1-P bind in the same location as does the allosteric effector AMP, near the monomer-monomer interface and some 30 A from the glucose site. At high concentrations glucose-1-P also binds strongly at the glucose site, with its phosphate only 7.2 A from that of the cofactor. Inorganic phosphate can also bind at this site. Implications for the participation of the pyridoxal phosphate in the catalytic mechanism are discussed in the light of these structural findings as well as the wealth of indirect evidence in the literature.
D001665:Binding Sites; D055598:Chemical Phenomena; D002621:Chemistry; D003067:Coenzymes; D008024:Ligands; D008958:Models, Molecular; D006005:Phosphorylases; D011732:Pyridoxal Phosphate / Q000032:analysis*; D014961:X-Ray Diffraction
D003067:Coenzymes; D008024:Ligands; D011732:Pyridoxal Phosphate; D006005:Phosphorylases
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