title: Location of pyridoxal phosphate in glycogen phosphorylase a.
abstract: 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.
mesh_terms: 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
chemical_list: D003067:Coenzymes; D008024:Ligands; D011732:Pyridoxal Phosphate; D006005:Phosphorylases
references.citation: Biochim Biophys Acta. 1957 Jul;25(1):16-21
references.pmid: 13445709
references.citation: Proc Natl Acad Sci U S A. 1977 Nov;74(11):4762-6
references.pmid: 270711
references.citation: Can J Biochem. 1977 Apr;55(4):465-73
references.pmid: 870152
references.citation: J Biol Chem. 1976 Oct 10;251(19):6142-6
references.pmid: 184094
references.citation: J Biol Chem. 1976 Nov 10;251(21):6852-9
references.pmid: 824288
references.citation: Biochemistry. 1971 Aug 3;10(16):3132-40
references.pmid: 5126929
references.citation: Biochem Biophys Res Commun. 1974 Apr 23;57(4):1166-74
references.pmid: 4830752
references.citation: J Mol Biol. 1968 Dec 14;38(2):245-7
references.pmid: 5760640
references.citation: J Biol Chem. 1972 Nov 10;247(21):6999-7004
references.pmid: 5082136
references.citation: Can J Biochem. 1973 Apr;51(4):344-56
references.pmid: 4696061
references.citation: Can J Biochem. 1970 Jul;48(7):746-54
references.pmid: 4397708
references.citation: Biochemistry. 1976 Jun 1;15(11):2394-401
references.pmid: 1276147
references.citation: J Mol Biol. 1976 May 5;103(1):1-13
references.pmid: 957422
references.citation: Biochemistry. 1975 May 6;14(9):2009-14
references.pmid: 1092346
references.citation: Can J Biochem. 1973 Jan;51(1):21-7
references.pmid: 4689092
references.citation: Fed Proc. 1966 Sep-Oct;25(5):1511-20
references.pmid: 5332191
references.citation: J Biol Chem. 1970 Nov 10;245(21):5560-8
references.pmid: 5528658
references.citation: Biochem Biophys Res Commun. 1970 Nov 9;41(3):594-600
references.pmid: 5529545
references.citation: Biochemistry. 1969 Dec;8(12):5189-96
references.pmid: 5391873
references.citation: Biochemistry. 1968 Oct;7(10):3590-608
references.pmid: 5681467
references.citation: Biochemistry. 1967 Dec;6(12):3695-710
references.pmid: 6076620
references.citation: Biochemistry. 1966 Jun;5(6):2117-25
references.pmid: 5963454
references.citation: Biochemistry. 1966 Sep;5(9):2906-11
references.pmid: 5961878
references.citation: Arch Biochem Biophys. 1966 Apr;114(1):216-22
references.pmid: 5954702