1k06
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1k06.gif|left|200px]] | [[Image:1k06.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1k06", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_1k06| PDB=1k06 | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Crystallographic Binding Study of 100 mM N-benzoyl-N'-beta-D-glucopyranosyl urea to glycogen phosphorylase b''' | '''Crystallographic Binding Study of 100 mM N-benzoyl-N'-beta-D-glucopyranosyl urea to glycogen phosphorylase b''' | ||
| Line 37: | Line 34: | ||
[[Category: Toth, B.]] | [[Category: Toth, B.]] | ||
[[Category: Zographos, S E.]] | [[Category: Zographos, S E.]] | ||
| - | [[Category: | + | [[Category: Catalytic site]] |
| - | [[Category: | + | [[Category: Glycogen phosphorylase]] |
| - | [[Category: | + | [[Category: New allosteric site]] |
| - | [[Category: | + | [[Category: Structure]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 22:08:10 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 19:08, 2 May 2008
Crystallographic Binding Study of 100 mM N-benzoyl-N'-beta-D-glucopyranosyl urea to glycogen phosphorylase b
Overview
Two substituted ureas of beta-D-glucose, N-acetyl-N'-beta-D-glucopyranosyl urea (Acurea) and N-benzoyl-N'-beta-D-glucopyranosyl urea (Bzurea), have been identified as inhibitors of glycogen phosphorylase, a potential target for therapeutic intervention in type 2 diabetes. To elucidate the structural basis of inhibition, we determined the structure of muscle glycogen phosphorylase b (GPb) complexed with the two compounds at 2.0 A and 1.8 A resolution, respectively. The structure of the GPb-Acurea complex reveals that the inhibitor can be accommodated in the catalytic site of T-state GPb with very little change in the tertiary structure. The glucopyranose moiety makes the standard hydrogen bonds and van der Waals contacts as observed in the GPb-glucose complex, while the acetyl urea moiety is in a favourable electrostatic environment and makes additional polar contacts with the protein. The structure of the GPb-Bzurea complex shows that Bzurea binds tightly at the catalytic site and induces substantial conformational changes in the vicinity of the catalytic site. In particular, the loop of the polypeptide chain containing residues 282-287 shifts 1.3-3.7 A (Calpha atoms) to accommodate Bzurea. Bzurea can also occupy the new allosteric site, some 33 A from the catalytic site, which is currently the target for the design of antidiabetic drugs.
About this Structure
1K06 is a Single protein structure of sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA.
Reference
Binding of N-acetyl-N '-beta-D-glucopyranosyl urea and N-benzoyl-N '-beta-D-glucopyranosyl urea to glycogen phosphorylase b: kinetic and crystallographic studies., Oikonomakos NG, Kosmopoulou M, Zographos SE, Leonidas DD, Chrysina ED, Somsak L, Nagy V, Praly JP, Docsa T, Toth B, Gergely P, Eur J Biochem. 2002 Mar;269(6):1684-96. PMID:11895439 Page seeded by OCA on Fri May 2 22:08:10 2008
Categories: Oryctolagus cuniculus | Phosphorylase | Single protein | Chrysina, E D. | Docsa, T. | Gergely, P. | Kosmopoulou, M. | Leonidas, D D. | Nagy, V. | Oikonomakos, N G. | Praly, J P. | Somsak, L. | Toth, B. | Zographos, S E. | Catalytic site | Glycogen phosphorylase | New allosteric site | Structure
