1kti: Difference between revisions
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'''BINDING OF 100 MM N-ACETYL-N'-BETA-D-GLUCOPYRANOSYL UREA TO GLYCOGEN PHOSPHORYLASE B: KINETIC AND CRYSTALLOGRAPHIC STUDIES''' | '''BINDING OF 100 MM N-ACETYL-N'-BETA-D-GLUCOPYRANOSYL UREA TO GLYCOGEN PHOSPHORYLASE B: KINETIC AND CRYSTALLOGRAPHIC STUDIES''' | ||
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==About this Structure== | ==About this Structure== | ||
1KTI 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 | 1KTI 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=1k0q 1k0q]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KTI OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Toth, B.]] | [[Category: Toth, B.]] | ||
[[Category: Zographos, S E.]] | [[Category: Zographos, S E.]] | ||
[[Category: | [[Category: Glycogenolysis]] | ||
[[Category: | [[Category: Type 2 diabetes]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 23:09:12 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 23:09, 2 May 2008
BINDING OF 100 MM N-ACETYL-N'-BETA-D-GLUCOPYRANOSYL UREA TO GLYCOGEN PHOSPHORYLASE B: KINETIC AND CRYSTALLOGRAPHIC STUDIES
OverviewOverview
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 StructureAbout this Structure
1KTI is a Single protein structure of sequence from Oryctolagus cuniculus. This structure supersedes the now removed PDB entry 1k0q. Full crystallographic information is available from OCA.
ReferenceReference
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 23:09:12 2008