1ftw: Difference between revisions

Revision as of 03:56, 1 July 2008

This article has been automatically seeded. Changes to this page should pertain to the PDB entry only and not to the protein or biomolecule in general.

File:1ftw.png

Template:STRUCTURE 1ftw

STRUCTURES OF GLYCOGEN PHOSPHORYLASE-INHIBITOR COMPLEXES AND THE IMPLICATIONS FOR STRUCTURE-BASED DRUG DESIGNSTRUCTURES OF GLYCOGEN PHOSPHORYLASE-INHIBITOR COMPLEXES AND THE IMPLICATIONS FOR STRUCTURE-BASED DRUG DESIGN

Template:ABSTRACT PUBMED 16222658

About this StructureAbout this Structure

1FTW is a Single protein structure of sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA.

ReferenceReference

Kinetic and crystallographic studies of glucopyranose spirohydantoin and glucopyranosylamine analogs inhibitors of glycogen phosphorylase., Watson KA, Chrysina ED, Tsitsanou KE, Zographos SE, Archontis G, Fleet GW, Oikonomakos NG, Proteins. 2005 Dec 1;61(4):966-83. PMID:16222658

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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-'''STRUCTURES OF GLYCOGEN PHOSPHORYLASE-INHIBITOR COMPLEXES AND THE IMPLICATIONS FOR STRUCTURE-BASED DRUG DESIGN'''
+===STRUCTURES OF GLYCOGEN PHOSPHORYLASE-INHIBITOR COMPLEXES AND THE IMPLICATIONS FOR STRUCTURE-BASED DRUG DESIGN===
-==Overview==
+<!--
-Glycogen phosphorylase (GP) is currently exploited as a target for inhibition of hepatic glycogenolysis under high glucose conditions. Spirohydantoin of glucopyranose and N-acetyl-beta-D-glucopyranosylamine have been identified as the most potent inhibitors of GP that bind at the catalytic site. Four spirohydantoin and three beta-D-glucopyranosylamine analogs have been designed, synthesized and tested for inhibition of GP in kinetic experiments. Depending on the functional group introduced, the K(i) values varied from 16.5 microM to 1200 microM. In order to rationalize the kinetic results, we determined the crystal structures of the analogs in complex with GP. All the inhibitors bound at the catalytic site of the enzyme, by making direct and water-mediated hydrogen bonds with the protein and by inducing minor movements of the side chains of Asp283 and Asn284, of the 280s loop that blocks access of the substrate glycogen to the catalytic site, and changes in the water structure in the vicinity of the site. The differences observed in the Ki values of the analogs can be interpreted in terms of variations in hydrogen bonding and van der Waals interactions, desolvation effects, ligand conformational entropy, and displacement of water molecules on ligand binding to the catalytic site.
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+{{ABSTRACT_PUBMED_16222658}}
 ==About this Structure==
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 [[Category: Inhibitor complex]]
 [[Category: Transferase]]
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