2f3q: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
|PDB= 2f3q |SIZE=350|CAPTION= <scene name='initialview01'>2f3q</scene>, resolution 1.96Å | |PDB= 2f3q |SIZE=350|CAPTION= <scene name='initialview01'>2f3q</scene>, resolution 1.96Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=PLP:PYRIDOXAL-5 | |LIGAND= <scene name='pdbligand=PLP:PYRIDOXAL-5'-PHOSPHATE'>PLP</scene> and <scene name='pdbligand=6GP:METHYL-N-(BETA-D-GLUCOPYRANOSYL)OXAMATE'>6GP</scene> | ||
|ACTIVITY= [http://en.wikipedia.org/wiki/Phosphorylase Phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.1 2.4.1.1] | |ACTIVITY= [http://en.wikipedia.org/wiki/Phosphorylase Phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.1 2.4.1.1] | ||
|GENE= | |GENE= | ||
| Line 30: | Line 30: | ||
[[Category: type 2 diabetes]] | [[Category: type 2 diabetes]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 15:03:52 2008'' | ||
Revision as of 16:03, 23 March 2008
| |||||||
| , resolution 1.96Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Phosphorylase, with EC number 2.4.1.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the glycogen phosphorylase B / methyl-N-(beta-D-glucopyranosyl)oxamate complex
OverviewOverview
Five oxalyl derivatives of beta-d-glucopyranosylamine were synthesized as potential inhibitors of glycogen phosphorylase (GP). The compounds 1-4 were competitive inhibitors of rabbit muscle GPb (with respect to alpha-d-glucose-1-phosphate) with K(i) values of 0.2-1.4 mM, while compound 5 was not effective up to a concentration of 10 mM. In order to elucidate the structural basis of their inhibition, we analysed the structures of compounds 1-4 in complex with GPb at 1.93-1.96 Angstrom resolution. The complex structures reveal that the inhibitors can be accommodated at the catalytic site at approximately the same position as alpha-d-glucose and stabilize the T-state conformation of the 280 s loop by making several favourable contacts to Asp283 and Asn284 of this loop. Comparison with the lead compound N-acetyl-beta-d-glucopyranosylamine (6) shows that the hydrogen bonding interaction of the amide nitrogen with the main-chain carbonyl oxygen of His377 is not present in these complexes. The differences observed in the K(i) values of the four analogues can be interpreted in terms of subtle conformational changes of protein residues and shifts of water molecules in the vicinity of the catalytic site, variations in van der Waals interactions, conformational entropy and desolvation effects.
About this StructureAbout this Structure
2F3Q is a Single protein structure of sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA.
ReferenceReference
Binding of oxalyl derivatives of beta-d-glucopyranosylamine to muscle glycogen phosphorylase b., Hadjiloi T, Tiraidis C, Chrysina ED, Leonidas DD, Oikonomakos NG, Tsipos P, Gimisis T, Bioorg Med Chem. 2006 Jun 1;14(11):3872-82. Epub 2006 Feb 7. PMID:16464598
Page seeded by OCA on Sun Mar 23 15:03:52 2008