2prj
From Proteopedia
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[[Image:2prj.jpg|left|200px]] | [[Image:2prj.jpg|left|200px]] | ||
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'''Binding of N-acetyl-beta-D-glucopyranosylamine to Glycogen Phosphorylase B''' | '''Binding of N-acetyl-beta-D-glucopyranosylamine to Glycogen Phosphorylase B''' | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2PRJ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. This structure supersedes the now removed PDB entry | + | 2PRJ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1prj 1prj]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PRJ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Watson, K A.]] | [[Category: Watson, K A.]] | ||
[[Category: Zographos, S E.]] | [[Category: Zographos, S E.]] | ||
| - | [[Category: | + | [[Category: Glycogen phosphorylase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 13:41:14 2008'' | |
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Revision as of 10:41, 4 May 2008
Binding of N-acetyl-beta-D-glucopyranosylamine to Glycogen Phosphorylase B
Overview
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.
About this Structure
2PRJ is a Single protein structure of sequence from Oryctolagus cuniculus. This structure supersedes the now removed PDB entry 1prj. Full crystallographic information is available from OCA.
Reference
N-acetyl-beta-D-glucopyranosylamine: a potent T-state inhibitor of glycogen phosphorylase. A comparison with alpha-D-glucose., Oikonomakos NG, Kontou M, Zographos SE, Watson KA, Johnson LN, Bichard CJ, Fleet GW, Acharya KR, Protein Sci. 1995 Dec;4(12):2469-77. PMID:8580837 Page seeded by OCA on Sun May 4 13:41:14 2008
