Summary for 2PRJ
| Entry DOI | 10.2210/pdb2prj/pdb |
| Descriptor | GLYCOGEN PHOSPHORYLASE, N-acetyl-beta-D-glucopyranosylamine, PYRIDOXAL-5'-PHOSPHATE, ... (5 entities in total) |
| Functional Keywords | glycogen phosphorylase, transferase |
| Biological source | Oryctolagus cuniculus (rabbit) |
| Total number of polymer chains | 1 |
| Total formula weight | 98107.76 |
| Authors | Oikonomakos, N.G.,Kontou, M.,Zographos, S.E.,Watson, K.A.,Johnson, L.N.,Bichard, C.J.F.,Fleet, G.W.J.,Acharya, K.R. (deposition date: 1998-12-11, release date: 1998-12-16, Last modification date: 2023-12-27) |
| Primary citation | Oikonomakos, N.G.,Kontou, M.,Zographos, S.E.,Watson, K.A.,Johnson, L.N.,Bichard, C.J.,Fleet, G.W.,Acharya, K.R. N-acetyl-beta-D-glucopyranosylamine: a potent T-state inhibitor of glycogen phosphorylase. A comparison with alpha-D-glucose. Protein Sci., 4:2469-2477, 1995 Cited by PubMed Abstract: Structure-based drug design has led to the discovery of a number of glucose analogue inhibitors of glycogen phosphorylase that have an increased affinity compared to alpha-D-glucose (Ki = 1.7 mM). The best inhibitor in the class of N-acyl derivatives of beta-D-glucopyranosylamine, N-acetyl-beta-D-glucopyranosylamine (1-GlcNAc), has been characterized by kinetic, ultracentrifugation, and crystallographic studies. 1-GlcNAc acts as a competitive inhibitor for both the b (Ki = 32 microM) and the a (Ki = 35 microM) forms of the enzyme with respect to glucose 1-phosphate and in synergism with caffeine, mimicking the binding of glucose. Sedimentation velocity experiments demonstrated that 1-GlcNAc was able to induce dissociation of tetrameric phosphorylase a and stabilization of the dimeric T-state conformation. Co-crystals of the phosphorylase b-1-GlcNAc-IMP complex were grown in space group P4(3)2(1)2, with native-like unit cell dimensions, and the complex structure has been refined to give a crystallographic R factor of 18.1%, for data between 8 and 2.3 A resolution. 1-GlcNAc binds tightly at the catalytic site of T-state phosphorylase b at approximately the same position as that of alpha-D-glucose. The ligand can be accommodated in the catalytic site with very little change in the protein structure and stabilizes the T-state conformation of the 280s loop by making several favorable contacts to Asn 284 of this loop. Structural comparisons show that the T-state phosphorylase b-1-GlcNAc-IMP complex structure is overall similar to the T-state phosphorylase b-alpha-D-glucose complex structure. The structure of the 1-GlcNAc complex provides a rational for the biochemical properties of the inhibitor. PubMed: 8580837PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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