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| - | [[Image:2prj.jpg|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_2prj| PDB=2prj | SCENE= }} | | {{STRUCTURE_2prj| PDB=2prj | SCENE= }} |
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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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| - | ==Overview==
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| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_8580837}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 8580837 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_8580837}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Zographos, S E.]] | | [[Category: Zographos, S E.]] |
| | [[Category: Glycogen phosphorylase]] | | [[Category: Glycogen phosphorylase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 13:41:14 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 08:39:24 2008'' |
Revision as of 05:39, 28 July 2008
Template:STRUCTURE 2prj
Binding of N-acetyl-beta-D-glucopyranosylamine to Glycogen Phosphorylase B
Template:ABSTRACT PUBMED 8580837
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 Mon Jul 28 08:39:24 2008
